Use the link below to share a full-text version of this article with your friends and colleagues. Learn more. This lecture dealing with comparative eye pathology will present various interesting animal eyes seen from a basic anatomical point of view but also seen as a potential animal eye model used for research. Anatomical differences in different animal eyes will be presented and nature's way of solving different eye problems is discussed.
Volume 95 , Issue S The full text of this article hosted at iucr. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account. If the address matches an existing account you will receive an email with instructions to retrieve your username.
Acta Ophthalmologica. Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article. Apoptosis regulated, physiological programmed cell death is distinct from necrosis uncontrolled cell death by lysis with inflammation. After axotomy RGC apoptosis is triggered primarily by the activation of caspase proteins.
Problem of Inherited Retinal Disease
Initiators such as caspase 8, 9, and 10 activate effectors such as caspase 3, 6, and 7 to cleave key cellular components and activate other degradative enzymes. Transient broad spectrum caspase inhibition by AAV adeno-associated virus -transduced p35 overexpression results in sustained RGC survival. Many prosurvival neurotrophic factors are also axogenic, but the underlying signaling mechanisms are distinct.
Activated glia in the retina and optic nerve produce multiple proregenerative neurotrophic factors. Activated macrophages enhance the neurotrophic effects of peripheral nerve and lens tissue. Animal models of open globe injury used to study retinal cell death and tissue regeneration damage the retina by incision, excision, or abrasion Table 3.
Death of non-RGC retinal components has been little studied in models of trauma. Photoreceptor apoptosis occurs in closed globe injury and cells of all retinal layers die adjacent to penetrating wounds Table 3. Retinal detachment, usually created by subretinal hyaluronic acid infusion, models components of the injury response outer retinal damage and ischemia; Table 3. Reattachment can be achieved by fluid—gas exchange. In the rabbit retina, all photoreceptors die, as do cells of the inner retina. The retinal response to detachment involves significant remodeling. Photoreceptor outer segments shorten within days deconstruction and mitochondria redistribute from the inner segments to the cell body.
Horizontal cells and RGC extend neurites throughout the retina and into the subretinal space. Retinal function after reattachment is reduced by altered synaptic connectivity, photoreceptor apoptosis, and imperfect outer segment regeneration especially cones , which is further impaired by subretinal scarring.
Researchers Restore Vision In an Animal Model of Childhood Blindness
RGC axons and retinal tissue regenerate in adult zebrafish Danio rerio , and this has been extensively studied in retinal excision, light injury, chemotoxicity, heat injury, and transgenic photoreceptor degeneration models. In embryonic chick and rat, excised retina regenerates from RPE. Thus, after injury, mammalian glia form scars and block the growth of regenerating axons, whereas zebrafish glia regenerate lost retinal tissue by generating new neurons.
There is a limited potential for mammalian glia to regenerate lost tissue and this can be enhanced by exogenous neurotrophins.
Mouse models of human ocular disease for translational research
Hydraulic and chemical RPE debridement leave Bruch's membrane intact; however, other injury methods damage Bruch's membrane and the choriocapillaris. RPE cells surrounding the denuded Bruch's membrane lose their polygonal shape and polarity and migrate to cover the defect by 4 days, with or without overlying neuroretina, and may form a pigmented monolayer when the neuroretina is present.
Raising a retinal detachment shears photoreceptor outer segments, which regenerate in the presence of RPE, 98 although some photoreceptors die. RPE excision or damage stimulates local cellular proliferation in rabbits and monkeys 97 , and peripheral RPE proliferation in pigs and rats, 54 , enhanced by subretinal amniotic membrane grafting or intravitreal FGF-2 injections. The choice of species for animal modeling of human diseases is based on considerations of comparative anatomy, availability, and the body of previous work, which allows comparison.
Comparison of the merangiotic rabbit retina with human inner retinal injury responses is tenuous. The small size, ease of husbandry and genetic manipulations, ready availability of antibodies for molecular studies, and similarities in retinal cellular and vascular structure to humans make murine rodents very attractive models of ocular trauma. Larger animals such as pigs and primates have anatomy comparable to that of humans and few scientific disadvantages.
Their use is limited by capital costs, husbandry, and ethical issues. Closed globe injury is achieved by moderate velocity impact, most commonly to sclera. A murine model would be ideal, but, of those reported, pig and primate models are the most suitable for translational studies. RGC death and axon regeneration are most commonly studied in murine models. Optic nerve transection causes the most aggressive cell death, although optic nerve crush leaves greater potential for axon regeneration. Rats and mice are suitable for open globe injury modeling, but when macular architecture is needed, primates are required.
Cone injury responses may be studied more effectively in rodents because cones are distributed throughout the retina.
Transscleral penetrating injuries release neurotrophins, causing PVR. Smaller wounds through the pars plana or anterior chamber reduce the risk of PVR and allow more defined retinal injuries, such as injuring retina but not RPE. RPE injury is studied in rabbits, cats, and pigs by RPE excision through a pars plana wound using either hydraulic debridement which preserves Bruch's membrane and the choriocapillaris, facilitating RPE resurfacing or debridement with silicone tubing or forceps which damages Bruch's membrane and the choriocapillaris, impairing RPE resurfacing.
Preserving the overlying neuroretina by injuring RPE under an induced retinal detachment also affects healing. RGC survival and long distance axon regeneration has been induced after axotomy, but regeneration is not functional and regenerative mechanisms have yet to be fully defined and clinically exploited. The mammalian retina and RPE can regenerate lost tissue from progenitor cells.
However, neither the cell death mechanisms in cells other than RGC nor strategies to enhance tissue regeneration after open or closed globe trauma have been extensively studied.
By Sara Cassidy, M.S., Ph.D.
Protection and induced regeneration of these tissues is an achievable goal requiring suitable animal models, such as those described here. The prevalence and 5-year incidence of ocular trauma. The Beaver Dam Eye Study. Br Med J. Ophthalmic injuries in British armed forces in Iraq and Afghanistan. Combat ocular trauma visual outcomes during operations Iraqi and Enduring Freedom. Remtulla S Hallett PE. A schematic eye for the mouse, and comparisons with the rat. Vision Res. Wikler KC Rakic P. Distribution of photoreceptor subtypes in the retina of diurnal and nocturnal primates.
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Animal models of optic nerve diseases
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