Purpose: To review the roles of the different vascular beds nourishing the inner retina [retinal ganglion cells (RGCs)] during normal development of the human eye, using our own tissue specimens to support our conclusions. Methods: An extensive search of the appropriate literature included PubMed, Google scholar, and numerous available textbooks. In addition, choroidal and retinal NADPH-diaphorase stained whole mount preparations were investigated. Results: The first critical interaction between vascular bed and RGC formation occurs in the sixth to eighth month of gestation leading to a massive reduction of RGCs mainly in the peripheral retina. The first 3 years of age are characterized by an intense growth of the eyeball to near adult size. In the adult eye, the influence of the choroid on inner retinal nutrition was determined by examining the peripheral retinal watershed zones in more detail. Conclusion: This delicately balanced situation of RGC nutrition is described in the different regions of the eye, and a new graphic presentation is introduced to combine morphological measurements and clinical visual field data.

This work describes completely new approach to detection of retinal nerve fibre layer (RNFL) loss in colour fundus images. Such RNFL losses indicate eye glaucoma illness and an early diagnosis of RNFL changes is very important for successful treatment. Method is presented with the purpose of supporting glaucoma diagnosis in ophthalmology. The proposed textural analysis method utilizes local binary patterns (LBP). This approach is characterized especially by computational simplicity and insensitivity to monotonic changes of illumination. Image histograms of LBP distributions are used to gain several textural features aimed to classify healthy or glaucomatous tissue of the retina. The method was experimentally tested using fundus images of glaucomatous patients with focal RNFL loss. The results show that the proposed method can be used in order to supporting diagnosis of glaucoma with satisfactory efficiency.

Indiana University-Purdue University Indianapolis (IUPUI) / Prevention of pathological angiogenesis is a key strategy for treatment of common blinding ocular diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. The current treatment strategies are associated with partial vision loss and are ineffective in a significant patient population. Hence novel drugs as well as new ways to target ocular angiogenesis are needed for treating these diseases. I pursued a natural antiangiogenic compound, cremastranone, to develop novel drug leads and to find new targets. The objective of my doctoral thesis project was to elucidate cremastranone’s molecular mechanism of action and optimize its structureactivity relationship (SAR). In order to achieve this goal, with the help of chemistry collaborators cremastranone was synthesized for the first time. I showed that cremastranone has 50-fold more potency against endothelial cells as compared to nonendothelial cells, and also tested a novel active isomer, SH-11052. By SAR studies I identified a potent molecule, SH-11037, that has 10-fold more selectivity against retinal endothelial cells as compared to macrovascular endothelial cells. I then elucidated cremastranone’s molecular mechanism using a chemical proteomic approach. I identified ferrochelatase (FECH) as a specific interacting protein partner of cremastranone using photoaffinity chromatography. Hence, I hypothesized that cremastranone exerts its antiangiogenic activities through modulation of the functions of FECH. Cremastranone inhibited the enzymatic activity FECH in endothelial cells. Therefore, I investigated the role of FECH in ocular angiogenesis. Partial loss of FECH, using a siRNA-based knock down approach, decreased retinal angiogenesis both in vitro and in vivo in mouse models. Knock down of FECH decreased the expression levels of key proangiogenic proteins HIF-1α, eNOS, and VEGFR2. This work suggests that ferrochelatase plays an important, previously undocumented role in angiogenesis and that targeting of this enzyme by cremastranone might be exploited to inhibit pathological angiogenesis in ocular diseases.

No description available.

La rétinopexie transsclérale est une technique de laser non invasive, visant à créer des ancrages de la rétine dans la choroïde, par la formation de multiples lésions de photocoagulation correspondant à des brulures focales reconnues comme cicatrices coagulatives atrophiques. Cette technique est utilisée chez l’humain, surtout chez l’enfant, en prévention d’un décollement de rétine. Malgré la procédure de laser, un re-décollement de la neurorétine est toujours possible. Cette technique est utilisée chez le chien, mais son application pourrait être utilisée sur un éventail d’espèces plus large, si un suivi des lésions de photocoagulation pouvait être effectué dans le temps afin de s’assurer de la conformité des cicatrices choriorétiniennes. La tomographie par cohérence optique (OCT), grâce à son grand pouvoir de résolution, de l’ordre de microns, pourrait être un outil efficace permettant de vérifier la structure des lésions de photocoagulation in vivo. À cet effet, notre étude a évalué la corrélation entre les coupes sagittales de lésion de photocoagulation, par histologie et OCT, en utilisant le lapin comme modèle animal. Notre étude a illustré la corrélation entre les images de photocoagulation à l’histologie et à l’OCT aux jours (J) 1, 7, 21 et 42 après le traitement laser. La diminution graduelle de la neurorétine, avec un aspect atrophique apparent dès J7, était visible dans les images d’histologie et d’OCT. L’hyperpigmentation histologique avait une claire correspondance avec l’hyper-brillance de la coupe OCT à J42. L’OCT semble être un outil précis et efficace pour le suivi d’une cicatrice choriorétinienne, effectuée au laser diode 810 nm. / Trans-scleral retinopexy is a non-invasive laser technique, aiming at anchoring the retina to the choroid, by producing multiple photocoagulation lesions corresponding to focal burns, named atrophic coagulating scars. This technique is used in humans, especially in children, to prevent retinal detachment. Despite the laser procedure, a re-detachment of the neuroretina is still possible. This technique is used mostly in dogs, but its application could be extended to other species, if a follow-up of the lesions could be carried out over time to ensure the conformity of the chorioretinal scars. Optical coherence tomography (OCT), thanks to its very high-resolution power, in the order of microns, could be an effective tool to evaluate photocoagulation lesions in vivo. For this purpose, a correlation between sagittal sections of photocoagulation lesions by histology and OCT was performed, using the rabbit as an animal model. Our study illustrated a comparison between histology and OCT photocoagulation images at days (D) 1, 7, 21 and 42 after laser treatment. The gradual decrease in neuroretinal thickness, with an atrophic appearance, was present as early as D7, and visible in both histology and OCT. The histological hyperpigmentation clearly corresponded to the hyper-brilliance of the OCT images at D42. The OCT appears to be a precise and effective tool for the follow-up over time of a chorioretinal scar, performed with an 810 nm diode laser.

No description available.

No / Retinal dystrophies are an overlapping group of genetically heterogeneous conditions resulting from mutations in more than 250 genes. Here we describe five families affected by an adult-onset retinal dystrophy with early macular involvement and associated central visual loss in the third or fourth decade of life. Affected individuals were found to harbor disease-causing variants in DRAM2 (DNA-damage regulated autophagy modulator protein 2). Homozygosity mapping and exome sequencing in a large, consanguineous British family of Pakistani origin revealed a homozygous frameshift variant (c.140delG [p.Gly47Valfs∗3]) in nine affected family members. Sanger sequencing of DRAM2 in 322 unrelated probands with retinal dystrophy revealed one European subject with compound heterozygous DRAM2 changes (c.494G>A [p.Trp165∗] and c.131G>A [p.Ser44Asn]). Inspection of previously generated exome sequencing data in unsolved retinal dystrophy cases identified a homozygous variant in an individual of Indian origin (c.64_66del [p.Ala22del]). Independently, a gene-based case-control association study was conducted via an exome sequencing dataset of 18 phenotypically similar case subjects and 1,917 control subjects. Using a recessive model and a binomial test for rare, presumed biallelic, variants, we found DRAM2 to be the most statistically enriched gene; one subject was a homozygote (c.362A>T [p.His121Leu]) and another a compound heterozygote (c.79T>C [p.Tyr27His] and c.217_225del [p.Val73_Tyr75del]). DRAM2 encodes a transmembrane lysosomal protein thought to play a role in the initiation of autophagy. Immunohistochemical analysis showed DRAM2 localization to photoreceptor inner segments and to the apical surface of retinal pigment epithelial cells where it might be involved in the process of photoreceptor renewal and recycling to preserve visual function.

published_or_final_version / Anatomy / Master / Master of Philosophy

Glaucoma is the second leading cause of blindness in the world. The disease is characterized by irreversible damage to retinal ganglion cells. Once glaucoma is detected, further vision loss can be prevented by pharmacological or surgical treatment. However, current diagnostic methods lack the necessary sensitivity and up to 40% of vision maybe irreversibly lost before detection occurs. A Swept Source Polarization-Sensitive Optical Coherence Tomography (SS-PSOCT) instrument for high sensitivity cross-sectional imaging of optical anisotropy in turbid media has been designed, constructed, and verified. A multiple-state nonlinear fitting algorithm was used to measure birefringence of the retinal nerve fiber layer with less than 1%± average uncertainty. To perform eye imaging efficiently a slit-lamp based interface for the SS-PSOCT instrument with a Line Scanning Laser Ophthalmoscope (LSLO) was used. This interface allowed for repeatable, stable, and registered measurements of the retina. A fixation target was used to stabilize the volunteer’s eye and image desired areas of the retina. The LSLO allowed for an optimization of the location of OCT scans on the retina and provided a fundus blood vessel signature for registration between different imaging sessions. The SS-PSOCT system was used to measure depth-resolved thickness, birefringence, phase retardation and optic axis orientation of the retinal nerve fiber layer in normal volunteers. The peripapillary area around the optic nerve head (ONH) is most sensitive to glaucoma changes and hence data was acquired as concentric ring scans about the ONH with increasing diameters from 2mm to 5mm. Imaging of normal patients showed that higher values of phase retardation occurred superior and inferior to the optic nerve head especially next to blood vessels and thicker parts of the retinal nerve fiber layer. / text

Background: High-density silicone oils are newly developed long-term tamponade agents for the treatment of complicated retinal detachment in the inferior retina. Previous studies describe satisfying anatomical and functional results. In this study we examined the largest cohort so far for a 9-month follow-up and performed a comparison to conventional silicone oil. Methods: Our study documents results and adverse effects after vitreoretinal surgery and endotamponade with Densiron® 68 in 99 cases of complicated retinal detachment. A 9-month follow-up was performed. Data of 21 patients with intraocular conventional silicone oil tamponade in complicated retinal detachment were retrospectively analyzed and served as control. Results: Anatomical success was achieved in 78 of 89 eyes (87.6%) with completed follow-up; visual acuity did not change significantly (from mean preoperative logMAR 1.88 to postoperative logMAR 1.96 (p = 0.9). Compared to control a higher anatomical success but a similar number of adverse effects were observed with heavy silicone oil in vitreous. Nevertheless, patients who received Densiron 68 twice due to redetachment showed a significantly higher rate of intraocular inflammation with the tamponade agent in situ. Conclusion: Our results support the hypothesis of Densiron 68 as potent tamponade agent for complicated retinal detachment in the inferior retinal segments especially in eyes where a previous operation failed. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.