S'estudien diferents aspectes relacionats amb les característiques anatòmiques, histològiques, ultraestructurals i morfomètriques de les estructures que formen l'òrgan de la visió de sis espècies d'insectívors (Sorex minutus, S. araneus, S. coronatus, Neomys fodiens, Crocidura russula i Talpa europaea) i de deu espècies de rosegadors (Clethrionomys glareolus, Arvicola terrestris, Chionomys nivalis, Microtus gerbei, M. duodecimcostatus, M. arvalis, Apodemus sylvaticus, Mus domesticus, M. Spretus i Eliomys quercinus) capturats en els seus hàbitats naturals. Els objectius concrets de la memòria consisteixen en relacionar les diferències i similituds interespecífiques de l'òrgan de la visió amb els hàbitats i els patrons d'activitat temporal de cada espècie, tant des del punt de vista funcional com filogenètic. En definitiva, es realitza un estudi sobre l'ecologia de la visió de les espècies considerades.Excepte a T. Europaea, a on apareixen estructures oculars en estat regressiu com a resposta a la seva activitat hipogea, els ulls de les espècies d'insectívors analitzades, estan ben desenvolupats, tot i les seves reduïdes dimensions. La còrnia està coberta per una capa multilaminar formada per cèl·lules mortes que podria augmentar l'índex de refracció de la còrnia i, per tant, el poder diòptric de l'ull. A més, presenten característiques que afavoreixen la visió diürna, com una distància nodal posterior del globus ocular proporcionalment gran, un cristal·lí voluminós però amb la cara posterior més aplanada que l'anterior, i un percentatge de cons que, en general, supera el 5% del total de cèl·lules fotoreceptores, particularment en els representants del gènere Sorex. En les espècies d'aquest mateix gènere s'ha detectat la presència de mitocondris gegants (megamitocondris) als el·lipsoides dels cons. En mamífers, aquests orgànuls només han estat descrits prèviament als cons de les retines del gènere Tupaia (Scandentia) i, probablement incrementen l'eficàcia òptica d'aquests fotoreceptors. L'ull de N. Fodiens mostra adaptacions oculars pròpies dels animals semiaquàtics, i li permeten veure-hi tant a dins com a fora de l'aigua. En el cas dels rosegadors, les espècies d'arvicolins estudiades mostren millors adaptacions a una visió crepuscular o diürna que els ulls dels murins considerats, particularment M. Arvalis. Així, la densitat de bastonets és inferior a la dels murins pel que la seva sensibilitat a la llum serà també inferior. Per contra, la proporció més elevada de cons els dotarà d'una major agudesa visual. A més, els ulls són proporcionalment més petits degut a la seva activitat cavadora. Els globus oculars d'A. Terrestris conserven característiques oculars, tant anatòmiques com morfomètriques que indicarien un primer origen semiaquàtic i diürn, seguides per una readaptació a les condicions de baixa il·luminació de l'interior de les galeries. En canvi, els murins mostren característiques oculars eminentment nocturnes, no només per la seva mida, els ulls d'A. Sylvaticus són tan grans que li sobresurten del cap, sinó també per la forma dels seus dioptris i l'estructura histològica de totes les túniques oculars, especialment de la retina.Els resultats obtinguts corroboren la relació entre la morfologia i la biometria de les estructures oculars amb els hàbits i els hàbitats de les espècies considerades. S'estableix que malgrat les reduïdes dimensions oculars, les modificacions en la mida i forma de l'ull i dels seus dioptris (còrnia i cristal·lí) permeten aconseguir una visió adequada per tal que les espècies estudiades puguin adaptar-se a diferents condicions de llum ambiental. També es constata que les espècies filogenèticament emparentades comparteixen un mateix model d'ull i que és aquest model el que ha anat variant, tant des del punt de vista biològic com òptic, per permetre una millor adaptació de les espècies a nous hàbitats.

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 229-253.

This research was a collaborative effort between the Air Force Research Laboratory (AFRL) and the University of Texas to examine the laser-tissue interaction of thermal lensing induced by continuous-wave, CW, near-infrared, NIR, laser radiation in the eye and its influence on the formation of a retinal lesion from said radiation. CW NIR laser radiation can lead to a thermal lesion induced on the retina given sufficient power and exposure duration as related to three basic parameters; the percent of transmitted energy to, the optical absorption of, and the size of the laser-beam created at the retina. Thermal lensing is a well-known phenomenon arising from the optical absorption, and subsequent temperature rise, along the path of the propagating beam through a medium. Thermal lensing causes the laser-beam profile delivered to the retina to be time dependent. Analysis of a dual-beam, multidimensional, high-frame rate, confocal imaging system in an artificial eye determined the rate of thermal lensing in aqueous media exposed to 1110, 1130, 1150 and 1318-nm wavelengths was related to the power density created along the optical axis and linear absorption coefficient of the medium. An adaptive optics imaging system was used to record the aberrations induced by the thermal lens at the retina in an artificial eye during steady-state. Though the laser-beam profiles changed over the exposure time, the CW NIR retinal damage thresholds between 1110-1319-nm were determined to follow conventional fitting algorithms which neglected thermal lensing. A first-order mathematical model of thermal lensing was developed by conjoining an ABCD beam propagation method, Beer's law of attenuation, and a solution to the heat-equation with respect to radial diffusion. The model predicted that thermal lensing would be strongest for small (< 4-mm) 1/e² laser-beam diameters input at the corneal plane and weakly transmitted wavelengths where less than 5% of the energy is delivered to the retina. The model predicted thermal lensing would cause the retinal damage threshold for wavelengths above 1300-nm to increase with decreasing beam-diameters delivered to the corneal plane, a behavior which was opposite of equivalent conditions simulated without thermal lensing. / text

The purpose of this research was to investigate detect and monitor laser-tissue interactions at threshold and potentially sub-threshold levels of injury. High resolution imaging modalities can provide a deeper understanding of candidate biomarkers disease and injury at the molecular, cellular, and tissue-levels which can be used to identify and diagnose early stages disease and damage. In addition, multi-scale and multi-modal imaging have also been used to identify inherent biomarkers of retinal disease and injury. Monitoring tissue changes can be mapped back to biological changes at the cellular and sub-cellular level. Diseases often alter tissue on the ultra-structural level yet retinal clinical diagnosis often monitor changes in tissue at the organ level. If injury and disease is detected and diagnosed during an “early” stage of development, treatments and drug interventions may prevent further spread of the pathology. Non-invasive imaging is expected to be a valuable tool for in vivo medical research as well as for the diagnosis and management of disease. In addition to developing new imaging tools and techniques to image the retina, the identification of inherent biomarkers of disease and health using diagnostic methods are almost equally as important. Using the inherent optical properties of retinal tissue, we can non- invasively quantify differences in the absorption and reflection of light to gauge the risk for visual disability or worse yet irreversible vision loss as a result of retinal disease and chronic light exposure. The research presented with in this dissertation is three separate studies aimed at identifying light injury and potential biomarkers indicating the risk of light mediated development of disease. / text

A high frequency of retinitis pigmentosa (RP) is found in Northern Sweden. In an inventory of autosomal recessive RP patients in Västerbotten County, a great number of cases with a unique phenotype was noticed, denoted Bothnia Dystrophy (BD). The aim of the study was to describe the phenotype, to determine the chromosomal location, and to identify the gene. Patients typically show night blindness from early childhood. Symptoms of defect macular function with a decrease of visual acuity can appear in early adulthood. The retinal fundus shows irregular white spots in a central, and parafoveal pattern along the arcades. Centrally areolar maculopathy develops and round circular atrophies are observed in the periphery. The disease was shown to be associated with a missense mutation in the RLBP1 gene resulting in an amino acid substitution (R234W) in the cellular retinaldehyde-binding protein (CRALBP). The R234W mutation was found in a homozygous state in 61 patients affected with BD. Ten patients were heterozygous for the R234W mutation, and presented a similar phenotype. No additional mutations in the coding sequence or exon-intron junctions were found. CRALBP is localised in retinal pigment epithelium (RPE), and Müller cells of the retina. In the RPE, CRALBP functions as a carrier protein for endogenous retinoids. Dark adaptometry and electrophysiologic testing showed an initial loss of rod function followed by a progressive reduction of the cone responses in older ages. A compromised rod function, dysfunction of the Müller cells, and indications of a disturbed function of the inner retina were found. With prolonged dark adaptation, a gradual increase in retinal sensitivity to light and an improvement of the ERG components occurred. The findings indicate a prolonged synthesis of photopigments, retardation of the visual process in the retinal pigment epithelium and a loss of retinal cells probably starting at a relative early age in BD. To evaluate the subjective visual function in BD patients, a battery of objective tests of visual function and composite score of the 25-item NEI-Visual Function Questionnaire (VFQ-25) were analyzed. We found that weighted distance logMAR visual acuity (WVA), had the strongest association with subjective visual function, and that there was a considerable loss of subjective and objective visual function with increasing age in BD patients. The prevalence of BD is as high as 1:3600 in Västerbotten County. The possibility that recycling of retinoids localized in the RPE might be impaired in BD might give future therapeutic possibilities. Due to the large and clinically well-characterized set of patients with this disease, they constitute a suitable study group.

Les nétrines sont une petite famille de protéines de guidage axonal qui peuvent attirer des axones ou en repousser d’autres lors du développement neuronal. Lors du développement de la rétine, les axones des cellules ganglionnaires de la rétine (CGR) sont attirés vers une source de nétrines au niveau du disque optique leur permettant de quitter la rétine et de former le nerf optique. Afin de pouvoir caractériser le rôle des nétrines dans le système visuel adulte, nous avons investigué l’expression des nétrines et leurs récepteurs dans la rétine de souris adulte. Alors qu’aucune expression de la nétrine-1 n’a été détectée dans la rétine adulte, l’expression de la nétrine-3 a été abondamment détectée au niveau des CGR et des cellules amacrines. Nous démontrons aussi que les récepteurs des nétrines sont exprimés dans la rétine adulte. Alors que DCC semble être confiné au niveau des axones des CGR, néogénine est retrouvé dans les dendrites des CGR et des cellules horizontales. Quant aux protéines de la famille des récepteurs homologues à UNC-5, UNC5B a été détecté dans les somas des CGR et UNC5C dans les cellules de Müller. La découverte que nétrine-3 et ses récepteurs sont abondamment exprimés dans plusieurs types cellulaires de la rétine adulte leur suggère un rôle dans le fonctionnement du système visuel mature. / The netrins are a small family of axonal guidance proteins that can attract or repulse growing axons during neural development. During development of the retina, retinal ganglion cells (RGCs) axons are attracted by a netrin source at the optic disc that permits them to exit the retina and form the optic nerve. To characterise the role of netrins in the adult visual system, we investigated the expression of netrins and their receptors in the adult mouse retina. While expression of netrin-1 has not been detected in the adult retina, netrin- 3 has been abundantly found in RGCs amacrine cells. We also demonstrate that netrin receptors are expressed in the adult retina. DCC was found to be restricted in RGCs axons and neogenin in dendrites of RGCs and horizontal cells. UNC5B proteins were detected at RGC soma and UNC5C proteins in the Müller cells. The finding that netrin-3 and its receptors are abundantly expressed in many cell types of the adult retina suggests a funtional role for them in the mature visual system.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Tennessee, Memphis, 2006. / The electronic version of this thesis is available at http://d.utmem.edu/CAMPUS-ACCESS-ONLY/2006-001-chona.pdf Includes bibliographical references (leaves 128-136).

Στόχος: Ο υποδοχέας του γλουταμινικού οξέος ΝMDA (N-methyl-D-aspartate), αποτελεί μόριο-κλειδί που διαμεσολαβεί πολλούς τύπους συναπτικής πλαστικότητας στο κεντρικό νευρικό σύστημα. Στο οπτικό σύστημα η πλαστικότητα ξεκινά στο επίπεδο του αμφιβληστοειδούς χιτώνα. Κατά την ανάπτυξη του αμφιβληστροειδούς οι υποδοχείς NMDA συμμετέχουν σε φαινόμενα πλαστικότητας εξαρτώμενα από την εμπειρία όπως ο λειτουργικός διαχωρισμός των ON και OFF μονοπατιών. Η ανάπτυξη και η οπτική αποστέρηση επηρεάζουν επίσης τις ηλεκτροφυσιολογικές ιδιότητες των υποδοχέων NMDA στον αμφιβληστροειδή του επίμυος καθώς και την έκφραση των υπομονάδων του NR1 και NR2. Η βασική υπομονάδα NR1 υφίσταται εναλλακτικό μάτισμα με αποτέλεσμα να εμφανίζεται σε οκτώ διαφορετικές ισομορφές που προσδίδουν μοριακή ποικιλότητα στον υποδοχέα. Το ερώτημα που ετέθη ήταν εάν η έκφραση των ισομορφών της υπομονάδας NR1 ρυθμίζεται κατά την ανάπτυξη του αμφιβληστροειδούς χιτώνα του επίμυος και εάν μεταβάλλεται από την οπτική εμπειρία. Μέθοδος: Χρησιμοποιήθηκαν αμφιβληστροειδείς επίμυων (Wistar) που μεγάλωσαν είτε σε φυσιολογικό ημερήσιο κύκλο 12 ώρες φως/12 ώρες σκοτάδι [normal-reared (NR)], είτε σε διαρκές σκοτάδι [dark-reared (DR)] από την 9η έως την 60η ημέρα μετά τη γέννηση. Η μελέτη της έκφρασης των ισομορφών του αμινοτελικού (NR1a, NR1b) και του καρβοξυτελικού (NR1-1, NR1-2, NR1-3, NR1-4) άκρου της υπομονάδας NR1 έγινε με τη μέθοδο της real-time PCR. Αποτελέσματα: Το αναπτυξιακό προφίλ όλων των ισομορφών εμφάνισε διαφορετική αύξηση κατά τη διάρκεια της δεύτερης και τρίτης εβδομάδας, με μέγιστη έκφραση στο τέλος της τρίτης εβδομάδας. Μεταξύ των ισομορφών του αμινοτελικού άκρου, η NR1b εκφραζόταν σταθερά σε υψηλότερα επίπεδα σε σχέση με την NR1a, ενώ μεταξύ των ισομορφών του καρβοξυτελικού άκρου, η NR1-2 εκφραζόταν σε υψηλότερα επίπεδα από την NR1-4, ενώ τόσο η NR1-1 όσο και η NR1-3 εκφράζονταν σε χαμηλά επίπεδα. Η ανάπτυξη στο σκοτάδι μείωσε την έκφραση όλων των ισομορφών σε πολλά αναπτυξιακά στάδια και στο ενήλικο ζώο. Σημαντική αλληλεπίδραση μεταξύ ηλικίας και οπτικής εμπειρίας προέκυψε για τις ισομορφές NR1a, NR1-2 και NR1-4. Συμπεράσματα: Η έκφραση όλων των ισομορφών της υπομονάδας NR1 μεταβάλλεται κατά την ανάπτυξη του αμφιβληστροειδούς του επίμυος, ενώ ορισμένες (NR1a, NR1-2 and NR1-4) ρυθμίζονται τόσο από την ηλικία όσο και από την οπτική εμπειρία. Τέτοιες μεταβολές μπορεί να παίζουν σημαντικό ρόλο σε φαινόμενα πλαστικότητας που λαμβάνουν χώρα στον αμφιβληστροειδή χιτώνα. / Purpose: The N-methyl-D-aspartate (NMDA) type of glutamate ionotropic receptor is a key molecule mediating plasticity related processes in the central nervous system. Visual system plasticity begins in the retina. During postnatal retinal development NMDA receptor has been shown to be involved in experience dependent plasticity such as the functional segregation of ON and OFF pathways. Development and visual deprivation have been found to affect the kinetics of NMDA receptor in rat retina and the expression of its main subunits NR1 and NR2. The NR1 fundamental subunit of NMDA receptor exists in eight distinct splice isoforms. Knowing that alternative splicing of the NR1 subunit offers a further molecular diversity to the receptor, we have addressed the question of whether the alternative splicing of NR1 subunit of the NMDA receptor is regulated during postnatal retinal development and whether this regulation is altered by visual experience. Methods: Retinas were dissected from eyes of Wistar rats raised either in normal 12-hour light/12-hour dark cycle [normal-reared (NR)], or in complete darkness [dark-reared (DR)] at postnatal days 9 to 60. Real-time PCR was performed in order to assess the mRNA expression of NR1 isoforms using oligonucleotide primers specific for N- terminal (NR1a, NR1b) and C-terminal splice variants (NR1-1, NR1-2, NR1-3, NR1-4). Results: The developmental profiles of mRNA expression levels of both N- and C-terminal NR1 isoforms showed differential increases during the second and third postnatal weeks, while their expression peaked at the end of the third week. Among N-terminal isoforms NR1b was constantly expressed at higher levels compared to NR1a and among the C-terminal isoforms, NR1-2 was expressed at higher levels than NR1-4, while both NR1-1 and NR1-3 were expressed at low levels. Dark-rearing led to reductions in both N- and C-terminal NR1 variants in several developmental ages and in adult retina. A significant age and experience interaction was observed at NR1a N-terminal isoform, and at the most abundant C-terminal isoforms NR1-2 and NR1-4. Conclusions: Our results have demonstrated that all NR1 splice isoforms are developmentally regulated in rat retina and some of them (NR1a, NR1-2 and NR1-4) are also bidirectionally regulated by age and visual experience. Such changes may play an important role in the plastic and activity-dependent events taking place in retina.