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Cells
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Animal Models of Retinal Degeneration
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Animal Models of Retinal Degeneration

A topical collection in Cells (ISSN 2073-4409).

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Editor

Prof. Dr. Steven J. Pittler

E-Mail Website
Collection Editor
Departmentof Optometry and Vision Science, Vision Science Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
Interests: photoreceptors; cyclic nucleotides; retinal degeneration; animal models; molecular neuroscience
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

The retina is an ideal CNS tissue to study because of its accessibility and the availability of many well-characterized animal models that exhibit ocular pathologies mimicking diseases seen in patients. The first successful gene therapy in the U.S. approved for use in patients was to treat a hereditary retinal degeneration called Leber congenital amaurosis, an early-onset form of the family of diseases collectively called retinitis pigmentosa. That pioneering achievement was based upon years of experimental studies using animal models of the human disease. There is still much to be done, and the recent development of new research tools for gene editing and other genome manipulations promises to bring an era of even greater accomplishments in the study and treatment of retinal diseases. With this new thematic collection, we aim to attract the most promising research in the field to drive further advancements that will ultimately lead to curative life-long interventions for the many hundreds of ocular disorders already known, as well as those yet to be discovered.

Prof. Steven J. Pittler
Collection Editor

Manuscript Submission Information

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Keywords

  • retinitis pigmentosa
  • age-related macular degeneration
  • amphibians
  • rodents
  • primates
  • gene editing
  • translational
  • transgenesis
  • review
  • transplantation
  • regeneration
  • clinical correlation

Published Papers (4 papers)

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2023

Jump to: 2021

25 pages, 15471 KiB  
Article
Intraocular Adeno-Associated Virus-Mediated Transgene Endothelin-1 Delivery to the Rat Eye Induces Functional Changes Indicative of Retinal Ischemia—A Potential Chronic Glaucoma Model
by Karin M. L. Nordahl, Vadim Fedulov, Anja Holm and Kristian A. Haanes
Cells 2023, 12(15), 1987; https://doi.org/10.3390/cells12151987 - 2 Aug 2023
Cited by 1 | Viewed by 2011
Abstract
Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy, and it has been utilized in animal models of retinal ischemia. The functional effects of long-term ET-1 exposure and possible compensatory mechanisms have, however, not been investigated. This was therefore [...] Read more.
Endothelin-1 (ET-1) overactivity has been implicated as a factor contributing to glaucomatous neuropathy, and it has been utilized in animal models of retinal ischemia. The functional effects of long-term ET-1 exposure and possible compensatory mechanisms have, however, not been investigated. This was therefore the purpose of our study. ET-1 was delivered into rat eyes via a single intravitreal injection of 500 µM or via transgene delivery using an adeno-associated viral (AAV) vector. Retinal function was assessed using electroretinography (ERG) and the retinal expression of potentially compensatory genes was evaluated by means of qRT-PCR. Acute ET-1 delivery led to vasoconstriction and a significant reduction in the ERG response. AAV–ET-1 resulted in substantial transgene expression and ERG results similar to the acute ET-1 injections and comparable to other models of retinal ischemia. Compensatory changes were observed, including an increase in calcitonin gene-related peptide (CGRP) gene expression, which may both counterbalance the vasoconstrictive effects of ET-1 and provide neuroprotection. This chronic ET-1 ischemia model might be especially relevant to glaucoma research, mimicking the mild and repeated ischemic events in patients with long-term vascular dysfunction. The compensatory mechanisms, and particularly the role of vasodilatory CGRP in mitigating the retinal damage, warrant further investigation with the aim of evaluating new therapeutic strategies. Full article
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2021

Jump to: 2023

20 pages, 5341 KiB  
Article
Generators of Pressure-Evoked Currents in Vertebrate Outer Retinal Neurons
by Ji-Jie Pang, Fan Gao and Samuel M. Wu
Cells 2021, 10(6), 1288; https://doi.org/10.3390/cells10061288 - 22 May 2021
Cited by 7 | Viewed by 2764
Abstract
(1) Background: High-tension glaucoma damages the peripheral vision dominated by rods. How mechanosensitive channels (MSCs) in the outer retina mediate pressure responses is unclear. (2) Methods: Immunocytochemistry, patch clamp, and channel fluorescence were used to study MSCs in salamander photoreceptors. (3) Results: Immunoreactivity [...] Read more.
(1) Background: High-tension glaucoma damages the peripheral vision dominated by rods. How mechanosensitive channels (MSCs) in the outer retina mediate pressure responses is unclear. (2) Methods: Immunocytochemistry, patch clamp, and channel fluorescence were used to study MSCs in salamander photoreceptors. (3) Results: Immunoreactivity of transient receptor potential channel vanilloid 4 (TRPV4) was revealed in the outer plexiform layer, K+ channel TRAAK in the photoreceptor outer segment (OS), and TRPV2 in some rod OS disks. Pressure on the rod inner segment evoked sustained currents of three components: (A) the inward current at <−50 mV (Ipi), sensitive to Co2+; (B) leak outward current at ≥−80 mV (Ipo), sensitive to intracellular Cs+ and ruthenium red; and (C) cation current reversed at ~10 mV (Ipc). Hypotonicity induced slow currents like Ipc. Environmental pressure and light increased the FM 1-43-identified open MSCs in the OS membrane, while pressure on the OS with internal Cs+ closed a Ca2+-dependent current reversed at ~0 mV. Rod photocurrents were thermosensitive and affected by MSC blockers. (4) Conclusions: Rods possess depolarizing (TRPV) and hyperpolarizing (K+) MSCs, which mediate mutually compensating currents between −50 mV and 10 mV, serve as an electrical cushion to minimize the impact of ocular mechanical stress. Full article
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21 pages, 5166 KiB  
Article
Rapid and Progressive Loss of Multiple Retinal Cell Types in Cathepsin D-Deficient Mice—An Animal Model of CLN10 Disease
by Mahmoud Bassal, Junling Liu, Wanda Jankowiak, Paul Saftig and Udo Bartsch
Cells 2021, 10(3), 696; https://doi.org/10.3390/cells10030696 - 21 Mar 2021
Cited by 11 | Viewed by 3841
Abstract
Vision loss is among the characteristic symptoms of neuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative lysosomal storage disorder. Here, we performed an in-depth analysis of retinal degeneration at the molecular and cellular levels in mice lacking the lysosomal aspartyl protease cathepsin D, an [...] Read more.
Vision loss is among the characteristic symptoms of neuronal ceroid lipofuscinosis (NCL), a fatal neurodegenerative lysosomal storage disorder. Here, we performed an in-depth analysis of retinal degeneration at the molecular and cellular levels in mice lacking the lysosomal aspartyl protease cathepsin D, an animal model of congenital CLN10 disease. We observed an early-onset accumulation of storage material as indicated by elevated levels of saposin D and subunit C of the mitochondrial ATP synthase. The accumulation of storage material was accompanied by reactive astrogliosis and microgliosis, elevated expression of the autophagy marker sequestosome 1/p62 and a dysregulated expression of several lysosomal proteins. The number of cone photoreceptor cells was reduced as early as at postnatal day 5. At the end stage of the disease, the outer nuclear layer was almost atrophied, and all cones were lost. A significant loss of rod and cone bipolar cells, amacrine cells and ganglion cells was found at advanced stages of the disease. Results demonstrate that cathepsin D deficiency results in an early-onset and rapidly progressing retinal dystrophy that involves all retinal cell types. Data of the present study will serve as a reference for studies aimed at developing treatments for retinal degeneration in CLN10 disease. Full article
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16 pages, 4810 KiB  
Article
A Comprehensive Study of the Retinal Phenotype of Rpe65-Deficient Dogs
by Matthew J Annear, Freya M Mowat, Laurence M Occelli, Alexander J Smith, Paul G Curran, James W Bainbridge, Robin R Ali and Simon M Petersen-Jones
Cells 2021, 10(1), 115; https://doi.org/10.3390/cells10010115 - 9 Jan 2021
Cited by 5 | Viewed by 3533
Abstract
The Rpe65-deficient dog has been important for development of translational therapies of Leber congenital amaurosis type 2 (LCA2). The purpose of this study was to provide a comprehensive report of the natural history of retinal changes in this dog model. Rpe65-deficient dogs from [...] Read more.
The Rpe65-deficient dog has been important for development of translational therapies of Leber congenital amaurosis type 2 (LCA2). The purpose of this study was to provide a comprehensive report of the natural history of retinal changes in this dog model. Rpe65-deficient dogs from 2 months to 10 years of age were assessed by fundus imaging, electroretinography (ERG) and vision testing (VT). Changes in retinal layer thickness were assessed by optical coherence tomography and on plastic retinal sections. ERG showed marked loss of retinal sensitivity, with amplitudes declining with age. Retinal thinning initially developed in the area centralis, with a slower thinning of the outer retina in other areas starting with the inferior retina. VT showed that dogs of all ages performed well in bright light, while at lower light levels they were blind. Retinal pigment epithelial (RPE) inclusions developed and in younger dogs and increased in size with age. The loss of photoreceptors was mirrored by a decline in ERG amplitudes. The slow degeneration meant that sufficient photoreceptors, albeit very desensitized, remained to allow for residual bright light vision in older dogs. This study shows the natural history of the Rpe65-deficient dog model of LCA2. Full article
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