Objetivos: Desenvolver um modelo de isquemia e reperfusão (I-R) ocular baseado no aumento da pressão intraocular (PIO) em ratos Wistar, e utilizar este modelo para investigar o efeito da guanosina (GUA) na captação de glutamato (GLU) nas retinas destes ratos em condições de I-R. Métodos: Desenvolvemos um modelo de I-R ocular e utilizamos este modelo para investigar 30 ratos Wistar, divididos em 3 grupos de 10 animais. Em cada rato, o olho direito foi submetido à elevação da PIO, gerando isquemia retiniana por 45 minutos, sem nenhuma intervenção no olho esquerdo (controle). No grupo 1, os animais não receberam GUA. No grupo 2, os animais receberam injeção intraperitoneal de GUA 30 minutos antes da isquemia e, no grupo 3, os animais receberam GUA na água durante 1 semana antes e 1 semana após a isquemia. Todos os animais foram mortos 7 dias após a isquemia e suas retinas foram coletadas para quantificar a captação de GLU. Resultados: As captações de GLU nas retinas controle foram semelhantes em todos os grupos. No grupo 1, a captação de GLU foi reduzida pela I-R. Esta redução foi abolida pela GUA administrada na água (grupo 3) e, no grupo 2, a captação de GLU aumentou com a administração intraperitoneal de GUA (P<0.001; ANOVA). Conclusões: Estes resultados sugerem que a I-R ocular gerada em nosso modelo experimental diminuiu a captação de GLU nas retinas de ratos Wistar e que a GUA aboliu tal redução ou, até mesmo, aumentou a captação de GLU. Este efeito da GUA está de acordo com estudos prévios que revelaram comportamento neuroprotetor da GUA no sistema nervoso central, por estimular a captação de GLU por astrócitos. Na retina, este efeito pode ser devido à ação da GUA estimulando a captação de GLU pelas células de Müller. / Purpose: To devise an experimental model of ocular ischemia-reperfusion (I-R) based on intraocular pressure (IOP) elevation in Wistar rats, and use this model to investigate the effect of guanosine (GUA) on glutamate (GLU) uptake in retinas of Wistar rats submitted to such ocular I-R injuries. Methods: We devised an experimental model of ocular I-R and applied this model to investigate 30 Wistar rats, divided in 3 groups of 10 rats. Each rat was submitted to IOP elevation in the right eye generating retinal ischemia during 45 minutes with no intervention in the left eye (control retina). In group 1, animals did not receive any GUA. In group 2, animals received an intraperitoneal injection of GUA 30 minutes before ischemia and, in group 3, animals received GUA in water during 1 week before and 1 week after ischemia. All animals were killed 7 days after ischemia and retina samples were obtained. Glutamate uptakes were performed from these retina samples. Results: GLU uptake in control retina was similar in all groups. In group 1, GLU uptake was significantly reduced by I-R; this reduction was abolished by GUA administration in water (group 3) and GLU uptake increased with intraperitoneal GUA (group 2).(P<0.001; ANOVA) Conclusions: These results point that I-R generated by our experimental model decreased GLU uptake in retinas of Wistar rats and that GUA abolished or even overcomed this decrease. These GUA effects are in agreement to previous results, which show that GUA administration presents neuroprotection in central nervous system by stimulating GLU uptake, mainly by astrocytes. In retina, this effect may be due to GUA stimulation of GLU uptake exerted mainly by Müller cells.

INTRODUÇÃO: O blefaroespasmo essencial é uma distonia focal caracterizada por contrações involuntárias, espasmódicas e bilaterais dos músculos protratores das pálpebras. O glaucoma é a principal causa de cegueira irreversível em adultos de países desenvolvidos e a elevação da pressão intra-ocular é o maior fator de risco para o desenvolvimento da doença. A contração voluntária forçada das pálpebras pode causar aumentos da pressão intra-ocular de até 90 mmHg. Uma vez que pacientes com blefaroespasmo essencial apresentam contrações palpebrais freqüentes e de forte intensidade, eles poderiam compor um grupo de risco para o desenvolvimento do glaucoma. MÉTODOS: Vinte e oito pacientes com blefaroespasmo essencial e 28 pacientes de grupo controle, formado por indivíduos com doenças palpebrais ou no seu pós-operatório, foram submetidos a um exame oftalmológico completo. No grupo de pacientes com blefaroespasmo, a avaliação foi realizada em 8 a 11 dias após o tratamento com toxina botulínica. Efetuou-se exame de refração e medida de melhor acuidade visual corrigida com tabela de Snellen, biomicroscopia em lâmpada de fenda, tonometria de aplanação, campo visual computadorizado, teste de sobrecarga hídrica e biomicroscopia de fundo para avaliação da papila óptica. RESULTADOS: 1) A prevalência de glaucoma nos pacientes com blefaroespasmo foi significativamente maior do que nos indivíduos do grupo controle, sendo diagnosticada em 14,3% e 3,6% dos casos, respectivamente (p=0,008). 2) A pressão intra-ocular foi significativamente maior nos pacientes com blefaroespasmo (15,80 ± 3,80 mmHg) do que nos indivíduos do grupo controle (13,90 ± 2,75 mmHg) (p= 0,004). 3) O pico da pressão intra-ocular na prova de sobrecarga hídrica foi significativamente maior nos pacientes com blefaroespasmo essencial (18,82 ± 4,47 mmHg) do que nos indivíduos do grupo controle (16,27 ± 2,69 mmHg) (p=0,0421). DISCUSSÃO: Diversos estudos descreveram a influência da compressão palpebral sobre a pressão intra-ocular. A prova de sobrecarga hídrica tem sido considerada uma ferramenta indireta para se avaliar a capacidade do fluxo de drenagem do trabeculado, além de exibir correlação com os picos de pressão intra-ocular que muitas vezes não são detectados em exames de rotina. Os pacientes com blefaroespasmo essencial apresentaram pressões intra -oculares e picos de pressão intra-ocular na prova de sobrecarga hídrica mais elevados do que os pacientes do grupo controle, o que poderia indicar um baixo fluxo de drenagem. Estas altíssimas variações de pressão intra -ocular a que estes indivíduos são submetidos constantemente, em pacientes com menor fluxo de drenagem poderiam causar um aumento crônico da pressão intra -ocular e o desenvolvimento do glaucoma. CONCLUSÕES: Os resultados observados sugerem que estes pacientes compõem um grupo de risco para o desenvolvimento de glaucoma e esta doença deve ser pesquisada de maneira sistemática na avaliação inicial e durante o seguimento desses casos / INTRODUCTION: Essential blepharospasm is a focal distonia characterised by involuntary, spasmodic, bilateral contractions of eyelid protractors. Glaucoma is the most important cause of irreversible blindness in adults in developed countries and high intraocular pressure is the major risk factor for development of the disease. Voluntary forced eyelid closure can produce an intraocular pressure increase of 90 mmHg. As patients with essential blepharospasm present frequent and strong eyelid contractions, they could be at risk for glaucoma development. METHODS: Twenty eight patients with essential blepharospasm and 28 patients of a control group, with eyelid diseases or in the post-operative period, were submitted to a complete ophthalmic examination. In the group of patiens with blepharospasm, the evaluation was done between 8 to 11 days after botulinum toxin treatment. We performed refractometry and best corrected visual acuity with Snellen chart, slitlamp biomicroscopy, applanation tonometry, automated perimetry, water drinking test and dilated funduscopy to evaluate optic discs. RESULTS: 1) Prevalence of glaucoma in patients with blepharospasm (14,3%) was higher than in the individuals from control group (3,6%) (p=0,008). 2) Intraocular pressure was higher in patients with blepharospasm (15,80 ± 3,80 mmHg) than in the individuals from control group (13,90 ± 2,75 mmHg) (p=0,004). 3) Intraocular pressure peaks in the water drinking test were higher in patients with essential blepharospasm (18,82 ± 4,47 mmHg) than in the individuals from control group (16,27 ± 2,69 mmHg) (p=0,0421). DISCUSSION: Several studies reported the influence of eyelid compression over intraocular pressure. The water drinking test has been considered as an indirect tool to measure outflow facility and it has good correlation with intraocular pressure peaks which are frequently missed in routine examinations. Patients with essential blepharospasm had higher mean intraocular pressures and intraocular pressure peaks in the water drinking test than patients from control group, which could indicate low outflow facility. These high intraocular pressure variations in patients with low outflow facility could increase the intraocular pressure chronically and lead to development of glaucoma. CONCLUSION: Our results suggest that patients with essential blepharospasm be at higher risks for development of glaucoma and this disease should be always investigated at presentation and during follow-up of these cases

A determinação da pressão intraocular (PIO) é fundamental no exame oftálmico. Atualmente, novos tonômetros, baseados em diferentes princípios, estão sendo continuamente desenvolvidos. O objetivo deste estudo foi estabelecer os valores de referência da PIO de coelhos adultos, sem efeito de tranquilizantes, mensurada com o tonômetro de rebote (Tonovet) e o de aplanação (Tono-Pen Avia). Também foi preconizada a mensuração da PIO ao longo do dia nesta espécie e a comparação dos resultados obtidos com os dois tonômetros. A PIO foi aferida ao longo do dia (6h, 9h, 12h, 15h e 18h) em 38 coelhos (76 olhos) da raça Nova Zelândia Branca, adultos, com idade média de seis meses, machos ou fêmeas, com massa corporal média de 3,5kg. Previamente, foi realizado teste da lágrima de Schirmer, prova da fluoresceína, biomicroscopia com lâmpada de fenda e oftalmoscopia direta em todos os animais. A tonometria de rebote foi realizada primeiro e, decorridos 10 minutos, foi instilado colírio anestésico e realizada a tonometria de aplanação. A PIO obtida utilizando as duas técnicas foi comparada estatisticamente. A média da PIO com o Tonovet foi de 9,51 ± 2,62 mmHg (variação de 3- 23mmHg) e 15,44 ± 2,16 mmHg (variação de 8 – 26mmHg) com o Tono-Pen Avia. Houve diferença estatística significante entre os valores obtidos com os dois tonômetros (P < 0,001). A relação entre os dois tonômetros foi representada através da equação de regressão linear: y = 0,4923x + 10,754 (y= Tonovet e x= Tono-Pen Avia). No início do dia foram registradas PIOs mais elevadas, mas a média dos valores ao longo do dia, com ambos os aparelhos, foi estatisticamente o mesmo (p = 0,086). O valor do coeficiente de correlação obtido foi r2= 0,357. Os resultados demonstram que o Tono-Pen Avia é mais variável e superestima a PIO de coelhos quando comparado ao Tonovet. Nas primeiras horas do dia, a PIO de coelhos foi mais alta que nos demais horários, independentemente do tonômetro utilizado. / The determination of intraocular pressure (IOP) is crucial in eye examination. Currently, new tonometers based on different principles are being continuously developed. The objective was to establish reference values of IOP of adults rabbits without the effect of tranquilizers, utilizing the rebound tonometer (Tonovet ) and the applanation tonometer (Tono-Pen Avia) for measurements. It also aimed to advocate the measurement of IOP throughout the day in this species and compare the results obtained with the two tonometers. The IOP was measured throughout the day (6h, 9h, 12h, 15h and 18h) in 38 New Zealand White rabbits (76 eyes), adults, males or females, with mean weight of 3.5kg and an average age of six months. Previously, the Schirmer tear test, fluorescein test, biomicroscopy with slit lamp and direct ophthalmoscopy were performed in all animals. First, the rebound tonometry was performed and after a minimum of 10 minutes anesthetic drops were instilled and applanation tonometry was carried out. IOP obtained using the two techniques was compared by statistical analysis. The average IOP was 9.51 ± 2.62 mmHg (range 3 - 23 mmHg) and 15.44 ± 2.16 mmHg (range 8 – 26mmHg), with Tonovet and Tono-Pen Avia, respectively. Statistic significant difference between the two tonometers was (P <0.001). The linear regression equation that describes the relationship between the two tonometers was: y = 0.4923 x + 10.754 (y= Tonovet e x= Tono-Pen Avia). Earlier in the day, higher IOPs were recorded, but the average behavior of IOP throughout the day with both devices was statistically the same (p = 0.086). The value of the correlation coefficient was r2 = 0.357. The results show that the Tono-Pen Avia is more variable and overestimates the IOP of rabbits when compared with the Tonovet. In the early hours, the IOP of rabbits was higher than at other times, regardless of the tonometer used.

Objetivos: Desenvolver um modelo de isquemia e reperfusão (I-R) ocular baseado no aumento da pressão intraocular (PIO) em ratos Wistar, e utilizar este modelo para investigar o efeito da guanosina (GUA) na captação de glutamato (GLU) nas retinas destes ratos em condições de I-R. Métodos: Desenvolvemos um modelo de I-R ocular e utilizamos este modelo para investigar 30 ratos Wistar, divididos em 3 grupos de 10 animais. Em cada rato, o olho direito foi submetido à elevação da PIO, gerando isquemia retiniana por 45 minutos, sem nenhuma intervenção no olho esquerdo (controle). No grupo 1, os animais não receberam GUA. No grupo 2, os animais receberam injeção intraperitoneal de GUA 30 minutos antes da isquemia e, no grupo 3, os animais receberam GUA na água durante 1 semana antes e 1 semana após a isquemia. Todos os animais foram mortos 7 dias após a isquemia e suas retinas foram coletadas para quantificar a captação de GLU. Resultados: As captações de GLU nas retinas controle foram semelhantes em todos os grupos. No grupo 1, a captação de GLU foi reduzida pela I-R. Esta redução foi abolida pela GUA administrada na água (grupo 3) e, no grupo 2, a captação de GLU aumentou com a administração intraperitoneal de GUA (P<0.001; ANOVA). Conclusões: Estes resultados sugerem que a I-R ocular gerada em nosso modelo experimental diminuiu a captação de GLU nas retinas de ratos Wistar e que a GUA aboliu tal redução ou, até mesmo, aumentou a captação de GLU. Este efeito da GUA está de acordo com estudos prévios que revelaram comportamento neuroprotetor da GUA no sistema nervoso central, por estimular a captação de GLU por astrócitos. Na retina, este efeito pode ser devido à ação da GUA estimulando a captação de GLU pelas células de Müller. / Purpose: To devise an experimental model of ocular ischemia-reperfusion (I-R) based on intraocular pressure (IOP) elevation in Wistar rats, and use this model to investigate the effect of guanosine (GUA) on glutamate (GLU) uptake in retinas of Wistar rats submitted to such ocular I-R injuries. Methods: We devised an experimental model of ocular I-R and applied this model to investigate 30 Wistar rats, divided in 3 groups of 10 rats. Each rat was submitted to IOP elevation in the right eye generating retinal ischemia during 45 minutes with no intervention in the left eye (control retina). In group 1, animals did not receive any GUA. In group 2, animals received an intraperitoneal injection of GUA 30 minutes before ischemia and, in group 3, animals received GUA in water during 1 week before and 1 week after ischemia. All animals were killed 7 days after ischemia and retina samples were obtained. Glutamate uptakes were performed from these retina samples. Results: GLU uptake in control retina was similar in all groups. In group 1, GLU uptake was significantly reduced by I-R; this reduction was abolished by GUA administration in water (group 3) and GLU uptake increased with intraperitoneal GUA (group 2).(P<0.001; ANOVA) Conclusions: These results point that I-R generated by our experimental model decreased GLU uptake in retinas of Wistar rats and that GUA abolished or even overcomed this decrease. These GUA effects are in agreement to previous results, which show that GUA administration presents neuroprotection in central nervous system by stimulating GLU uptake, mainly by astrocytes. In retina, this effect may be due to GUA stimulation of GLU uptake exerted mainly by Müller cells.

A aferição da pressão intraocular (PIO) é fundamental durante o exame oftálmico. Objetivou-se estabelecer os valores de referência da PIO de chinchilas de diferentes faixas etárias utilizando o tonômetro de rebote. A PIO foi aferida ao longo do dia às 7, 12 e 19 horas utilizando o tonômetro de rebote (Tonovet®). As chinchilas foram subdivididas em três grupos com 12 animais cada, considerando as idades, designados por GI (animais com idade entre dois a seis meses), GII (com idade entre 20 e 34 meses) e GIII (animais com idade entre 37 e 135 meses). Previamente, foram realizados teste da lágrima de Schirmer, prova da fluoresceína, biomicroscopia com lâmpada de fenda e oftalmoscopia indireta em todos os animais. O valor médio da pressão intraocular encontrado foi 2,49 ± 0,56 mmHg, os valores médios para o grupo I foi de 2,47±0,581 mmHg, no grupo II de 2,47±0,581 mmHg e no grupo III de 2,51±0,531 mmHg. Não foram encontradas diferenças significativas entre a idade e a PIO (P = 0,756). Não foram encontradas diferenças significativas entre as horas do dia e a PIO (P = 0,415). Não foram encontradas diferenças significativas entre os sexos (P = 0,857). Os valores da PIO em chinchilas não sofrem alterações decorrentes do sexo e da idade dos animais. Não ocorre influência do ritmo circadiano na PIO de chinchilas. / The assessment of intraocular pressure (IOP) is essential for the ocular examination. The purpose of this study was to establish reference values of intraocular pressure chinchillas (Chinchilla lanigera) of different age groups. Thirty-six Chinchillas were divided in three groups of 12 animals each, considering the ages designated by GI (animals aged two to six months), GII (aged between 20 and 34 months) and GIII (animals aged between 37 and 135 months). Intraocular pressure was measured at 7, 12 and 19 hours. Tear production was measured, fluorescein test, slit-lamp biomicroscopy and indirect ophthalmoscopy in all animals and IOP was measured using the rebound tonometer (Tono Vet®) set on the P (undefined species) setting, with measurements obtained from each eye. No abnormalities were found on ophthalmic examination. The mean (±SD) of IOP was 2.49 ± 0.56 mmHg, with a range of 2-4 mmHg. The mean (±SD) of IOP for group I, II and III were 2.47 ± 0.581 mmHg, 2.47 ± 0.581 mmHg and 2,51 ± 0.531 mmHg, respectively. No significant differences were found between age and IOP and no significant differences were found between the hours of day and IOP. No significant differences were found between the genders. The IOP in chinchillas is unchanged between genders and age of the animals. The circadian rhythm is not influenced by IOP in chinchillas.

A diabetes mellitus (DM) causa alterações em todas as camadas da córnea. Córneas de pacientes diabéticos têm controle de sua hidratação prejudicado e são mais propensas à descompensação após injúria. A uveíte faco-induzida (UFI) ocorre em grandes proporções associada à catarata hipermatura em cães. A UFI também acarreta danos ao endotélio da córnea e pode levar ao edema estromal, usualmente transitório. Cães diabéticos são particularmente predispostos ao desenvolvimento de catarata e UFI associada. Os efeitos da DM e UFI podem potencialmente vir a se somar em córneas de cães com catarata diabética. A pressão intra-ocular (PIO) e paquimetria podem ser ferramentas úteis na determinação dessas alterações. O objetivo deste estudo foi determinar a relação entre pressão intra-ocular e paquimetria nos diferentes estágios de desenvolvimento das cataratas diabéticas e não diabéticas em cães da raça Poodle. Cento e vinte e dois cães adultos da raça Poodle, 134 fêmeas e 99 machos, com idades de 2 a 16 anos, foram admitidos no Serviço de Oftalmologia do Hospital Veterinário da Universidade de São Paulo e incluídos no trabalho. Afecções oculares concomitantes, ou doenças sistêmicas com manifestação ocular, foram consideradas fatores de exclusão. Após exame clínico oftalmológico, coletou-se dados referentes ao tempo de leucocoria e tempo de desenvolvimento da DM. Os cães tiveram a PIO mensurada por meio do TonoPen-XL® e a paquimetria mensurada com o uso do PachPen®. Para isso realizou-se anestesia tópica (colírio de Proximetacaína a 0,5% - Anestalcon®, Alcon). As comparações estatísticas entre as variáveis foram realizadas utilizando os testes de Spearman, Mc-Nemar e Mann-Whitney quando apropriados. As distribuições das variáveis entre os grupos foram avaliadas pelo test de Kruskal-Wallis, e quando significantes, o teste de Dunn foi utilizado para descriminar as diferenças encontradas. O nível de significância foi estabelecido em p<0,05. Dos 122 cães, 233 olhos foram incluídos e classificados em grupo controle (n=39), catarata incipiente (n=20), imatura (n=29), matura (n=20), hipermatura (n=80), catarata diabética imatura (n=9), diabética matura (n=11) e diabética hipermatura (n=25). As distribuições das variáveis (sexo, idade, peso, presença de uveíte, tempo de leucocoria, PIO e paquimetria) foram estatisticamente diferentes entre os diversos grupos. Fêmeas apresentaram-se mais acometidas por catarata diabética. A idade média dos animais variou de 7,03 a 10,73 anos entre os grupos, e os animais diabéticos foram estatisticamente mais velhos. A PIO foi estatisticamente menor e os sinais clínicos de UFI mais prevalentes nos grupos de cataratas hipermaturas, tanto diabéticas, quanto não diabéticas. A PIO correlacionou-se negativamente com a idade e a paquimetria. Houve correlação positiva da paquimetria com a idade e o peso; e correlação negativa com o tempo de leucocoria e a PIO. Olhos acometidos por UFI tiveram PIO estatisticamente menor e paquimetria maior, com diferença de 2 mmHg e 60 µm, respectivamente. Nos cães acometidos por catarata diabética, a paquimetria encontrou-se particularmente aumentada, e a UFI particularmente presente. Esse aumento possivelmente reflete a somatória dos efeitos da DM e UFI sobre a córnea. A hipermaturidade foi correlacionada à presença da UFI. A PIO e paquimetria mostraram-se instrumentos valiosos na determinação da UFI, principalmente se forem negativamente correlacionadas entre si. / Diabetes mellitus (DM) causes different alterations in all corneal layers, such as deficient control of hydration, what makes them prone to decompensate after injury. Lens induced uveitis (LIU) occurs mainly in dogs presenting hypermature cataracts, what causes irreversible damages to the corneal endothelium and may lead to stromal edema, usually transient. DM dogs are particularly predisposed to cataract with LIU associated. Intraocular pressure (IOP) and pachymetry measurements may be useful procedures capable to detect such alterations. The aim of this study was to determinate the relationship between intraocular pressure and pachymetry on diabetic and nondiabetic Poodles, presenting different stages of cataracts. One hundred twenty-two Poodles, 134 females and 99 males, with ages varying from 2 to 16 years, were admitted at the Ophthalmology Service, of the Veterinary Hospital, of the University of São Paulo. After complete identification of the animals, anamnese (time of DM and cataract formation) and ophthalmological exam, dogs were included in the study. Dogs affected by other systemic diseases inducing ocular manifestation or other primary ocular alteration were excluded. LIU was diagnosed by observation of congestion of the episcleral vases and resistence to midriasis after induction with Mydriacyl®. IOP was measured by TonoPen-XL® and pachymetry by PachPen® after instillation of anesthetic eyedrop (Proximetacaine 0,5% - Anestalcon, Alcon). Statistical comparison between factors were made using Spearman, Mc-Nemar and Mann-Whitney tests when appropriated. The distributions of the factors among the groups were compared by Krusskal-Walliss test, and when significant, Dunns test was used to describe the differences found. The level of significance was set at p<0,05. Two hundred thirty-three eyes of 122 Poodles were evaluated. Eyes were classified in different groups: healthy dogs without cataracts (n=39); dogs presenting incipient cataract (n=20); with immature cataracts (n=29); mature cataracts (n=20); or hypermature cataracts (n=80); DM dogs presenting immature cataract (n=9); DM with mature cataracts (n=11); and DM with hypermature cataracts (n=25). Distribution of factors, such as age, sex, weight, time of DM and cataract, presence of LIU, IOP and pachymetry were statistically different between groups. Female Poodles were more affected by diabetic cataract and diabetic dogs were older than the other ones. IOP was statistically lower and LIU alterations more prevalent in the hypermature cataract groups (diabetic and no diabetics). IOP was negatively correlated to age and pachymetry measures. Pachymetry was positively correlated to age and weight. Negative correlation was observed between pachymetry and time of cataracts formation. LIU eyes presented lower IOP and higher pachymetry. The difference found at pachymetry and IOP measurements in LIU and non LIU eyes were 60 µm and 2 mmHg respectively. In diabetic dogs, pachymetry was particularly higher and LIU particularly present. The higher corneal thickness may possible be related to the sum of alterations caused by DM and LIU to those corneas. Hypermaturity was directly related to LIU. We concluded that pachymetry and IOP measurements are important procedures to the LIU diagnosis, mainly when negatively correlated.

A selective a2-adrenergic agonist, lofexidine, significantly reduced intraocular pressure (lOP) in intact ocular normotensive NZW rabbits, producing a differential dose-dependent decrease in IOP in'the ipsilateral and contralateral eye. Contralateral IOP reduction was most observable at low doses. Unilateral superior cervical ganglionectomy and extraocular muscle excision studies were undertaken to elucidate the factors influencing differential IOP reduction by lofexidine. Similar significant contralateral decreases in IOP were noted when the agent was applied to either the intact or operated eye. Biochemical studies demonstrated that lofexidine inhibited isoproterenol-stimulated adenylcyclase in isolated iris-ciliary body preparations. Yohimbine, an α2-adrenergic antagonist, blocked this inhibitory response. Hence, these observations suggested that lofexidine's site of IOP reduction was probably at the cellular level.

Purpose: The aim of the study was to quantify the isolated tear film adhesion error in a Goldmann applanation tonometer (GAT) prism and in a correcting applanation tonometry surface (CATS) prism. Methods: The separation force of a tonometer prism adhered by a tear film to a simulated cornea was measured to quantify an isolated tear film adhesion force. Acrylic hemispheres (7.8 mm radius) used as corneas were lathed over the apical 3.06 mm diameter to simulate full applanation contact with the prism surface for both GAT and CATS prisms. Tear film separation measurements were completed with both an artificial tear and fluorescein solutions as a fluid bridge. The applanation mire thicknesses were measured and correlated with the tear film separation measurements. Human cadaver eyes were used to validate simulated cornea tear film separation measurement differences between the GAT and CATS prisms. Results: The CATS prism tear film adhesion error (2.74 +/- 0.21 mmHg) was significantly less than the GAT prism (4.57 +/- 0.18 mmHg, p<0.001). Tear film adhesion error was independent of applanation mire thickness (R-2=0.09, p=0.04). Fluorescein produces more tear film error than artificial tears (+0.51 +/- 0.04 mmHg; p<0.001). Cadaver eye validation indicated the CATS prism's tear film adhesion error (1.40 +/- 0.51 mmHg) was significantly less than that of the GAT prism (3.30 +/- 0.38 mmHg; p=0.002). Conclusion: Measured GAT tear film adhesion error is more than previously predicted. A CATS prism significantly reduced tear film adhesion error by similar to 41%. Fluorescein solution increases the tear film adhesion compared to artificial tears, while mire thickness has a negligible effect.

It is widely known that Central Corneal Thickness (CCT) and Radius of Curvature (RoC) in uence the estimated IntraOcular Pressure (IOP) obtained from Goldmann Applanation Tonometry (GAT). However, not much is known about the in uence of corneal material properties, especially in a clinical setting. Several numerical studies have been conducted in an attempt to quantify the in uence of corneal material properties on the IOP. These studies agree that corneal material properties do in uence the estimated IOP, which contradict the initial premise on which GAT was designed, namely that material properties do not in uence the obtained GAT readings. Also, there is no consensus among these studies with respect to corneal material properties, thus a wide range of proposed properties exist. A possible explanation for this range of available corneal properties is the numerical modi elling assumptions used, which seem to be quite different. Different sets of experimental in ation test data were used to calibrate the constitutive models and different limbal boundary conditions were applied to simulate the experimental setup as well as in vivo conditions during GAT simulations. Therefore the purpose of this study is to determine whether these modelling assumptions in uence the obtained IOP and ultimately the overall conclusions. A Finite Element (FE) model of the human cornea is developed, implementing a constitutive model to represent the complex corneal structure and two limbal boundary conditions. This model is then calibrated using two different sets of experimental in ation test data. During calibration of the fibre reinforced elastic constitutive model it is found that independent of the assumptions made regarding the material coe cients, that the numerical in ation data compare well with the experimental data for all cases. Using this model a GAT simulation is conducted to estimate the IOP and the in uence of the modelling assumptions, cornea geometry and material properties are then investigated. The results indicate that the modelling assumptions, cornea geometry and material properties do infuence the estimated IOP. However, when assuming the cornea ground substance stiffness to be constant, it is found that the in uence on IOP due to material properties is not as significant. A correction equation is also proposed to account for the corneal geometric properties by calibrating the numerical model for a numerically normal cornea. This is done by utilising the various data sets which are obtained during the calibration of the constitutive model with the experimental inflation test data. It is concluded that using only inflation data to calibrate the constitutive model is not sufficient to uniquely describe the corneal material. This is evident as different material data sets are obtained, even though the experimental inflation data is matched well for a variety of considered cases. Each of these material data sets, in conjunction with geometric properties, yield different estimates for IOP during GAT simulations. This study therefore recommends the use of additional experimental data, such as strip extensometry, along with inflation test data to adequately calibrate a numerical model. It should also be noted that when modelling GAT care should be taken when considering the choice of limbal boundary condition, experimental data for calibration and assumptions made with regards to material coe cients, as these choices could potentially influence the outcomes and conclusions of a study. / Dissertation (MEng)--University of Pretoria, 2014. / gm2014 / Mechanical and Aeronautical Engineering / unrestricted

Le glaucome est une neuropathie optique associée à une augmentation de la pression intraoculaire (PIO). L’élévation de la PIO est due à la dégénérescence progressive du trabéculum. Les traitements antiglaucomateux vise à réduire la PIO, cependant il n’existe aucun traitement ciblant la dégénérescence du trabéculum. Les cellules souches mésenchymateuses (CSMs) sont utilisées comme outils thérapeutiques dans différentes pathologies dégénératives. Elles sécrètent un panel de molécules qui sont décrit comme atténuant les processus dégénératifs. L’objectif de ce travail a été d’évaluer l’intérêt des CSMs dans la prise en charge du glaucome. La caractérisation des CSMs ont été mis au point à partir de culture primaire de moelle osseuse de rat. En parallèle, un modèle expérimental de glaucome par cautérisation des veines épisclérales (EVC) a été réalisé. Nous nous sommes intéressés à l’effet de l’injection intracamérulaire des CSMs dans ce modèle. Les CSMs sont retrouvées incorporées aux tissus autour et dans le trabéculum. Les résultats obtenus in vivo montrent une diminution de la PIO par l’injection des CSMs préservant ainsi les cellules ganglionnaires périphériques de la rétine (CGRs). Par une approche in vitro, nous avons également caractérisé les effets du sécrétome des CSMs sur les cellules impliquées dans la pathologie glaucomateuse: les cellules trabéculaires et les cellules ganglionnaires de la rétine. Ces résultats ont permis de montrer que l’injection intracamérulaire de CSMs permettrait de protéger la fonction de régulation de la PIO et de protéger les CGRs dont la mort est responsable de la diminution de l’acuité visuelle chez le patient glaucomateux. / Glaucoma is a sight-threatening retinal neuropathy associated with elevated intraocular pressure (IOP) due to degeneration and fibrosis of the trabecular meshwork (TM). Glaucoma medications aim to reduce IOP without targeting the specific TM pathology, which could explain treatment failure observed in some cases. Bone-marrow mesenchymal stem cells (MSCs) are used today in various clinical studies to treat various degenerative processes. Here, we investigated the potential of MSC therapy in an ocular hypertension model. We demonstrated a rapid and long-lasting in vivo effect of MSC transplantation that significantly reduced IOP in hypertensive eyes induced by episcleral vein cauterization (EVC). MSCs were found located to the ciliary processes and the TM and are able to survive at these places. Enumeration of retinal ganglion cells (RGCs) on whole flat-mounted retina highlighted a protective effect of MSCs on RGC death. In vitro, the effect of MSC-conditioned medium (MSC-CM) on both the primary human trabecular meshwork (hTM) and RGCs showed that MSC-CM promotes: (i) hTM survival by activating the antiapoptotic pathway, Akt, (ii) hTM decontractibility as analyzed by the decrease in myosin phosphorylation and (iii) inhibition of TGF-β2-dependent profibrotic phenotype acquisition in hTM, (iiii) RGC survival and neuritic outgrowth in vitro. Finally, MSCs injection in the ocular anterior chamber in a rat model of ocular hypertension provides a neuroprotective effect in the glaucoma pathophysiology directly on RGC and indirectly via TM protection. These results originally demonstrate that MSCs represent promising tool for treating ocular hypertension and retinal cell degeneration.