An insight on established retinal injury mechanisms and prevalent retinal stem cell activation pathways in vertebrate models

Abstract

The brain processes visual information when light energy transduces into neural activity in the retina. The close-knit components of the central nervous system (CNS), the brain, and its extension retina are thus the critical players in visual perception, thereby aiding in daily activities. While the brain remains well protected inside the skull, the eyes are quite susceptible to physical injuries and chemical accidents. 1 Furthermore, one's genetic makeup and increasing age also invite multiple numbers of eye diseases such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), glaucoma, etc All this has contributed to the recent "World Reports on vision (2019)," which shows that a whopping 2.2 billion people globally fell victim to visual impairment in the past year. 2 The discovery of the existence of adult retinal stem/progenitor cells among different vertebrate species 3 and its high reparative activity in the case of lower vertebrates has presented us with a possibility to "self-heal" the retina one day. 4 Consequently, high regeneration competent animals, which include the amphibian newts and Xenopus, teleost zebrafish (Danio rerio), and chick are thus being explored 5 to investigate different genetic and epigenetic features, signaling pathways, and factors 6,7 that regulate stem cell activation, thus gradually filling in the gaps of our knowledge of mammals, which appear to be the least competent among the group. 8 With the hope of updating and giving researchers an idea about how these animal models have significantly shaped our understanding of the retinal regeneration process, in this review,

Retina regeneration: lessons from vertebrates

“…In the solution, 6-OHDA converts to quinone, which stimulates the production of free radicals. For using relatively high doses of 6-OHDA, sodium ascorbate in the solution prevents the free radical formation and hence non-specific damage [ 25 , 44 ]. Tunicamycin is an antibiotic inhibiting N-glycosylation of asparagine-linked oligosaccharides [ 45 ].…”

“…Light-induced damage follows the disruption of the standard light and dark cycle to a long dark cycle followed by exposure to high-intensity visible light [ 56 ] or ultraviolet light [ 57 ]. The light-induced damage is with tungsten halogen lamps, metal halide lamps and fiber optics [ 25 ]. Photothermal, photochemical and photomechanical mechanisms can mediate light-induced damage.…”

“…Depending on the extent of damage, cells may undergo apoptosis, necrosis or immediate cell death [ 55 ]. This kind of injury occurs in laser light photocoagulation and optical coherence tomography-guided laser injuries [ 25 ]. Photochemical damage is caused by oxygen free radicals.…”

“…These free radicals lead to the oxidation of polyunsaturated fatty acids and protein moieties that break down membranous structures. Retinal photoreceptors, especially outer segments, possess large amounts of membranes and are hence more susceptible to free radical-mediated damage [ 25 , 55 ]. Rapid introduction of energy into melanosomes generates mechanical compressive and tensile forces, causing photomechanical damage.…”

Pigment Epithelia of the Eye: Cell-Type Conversion in Regeneration and Disease

“…The launch of the molecular “rescue mechanisms”, discussed in detail in the review by Grigoryan E. [ 150 ], is also a common feature. The similarity can also be seen in the trigger effect of the components of the immune and circulatory systems [ 256 , 268 ], which, however, differ significantly between lower and higher vertebrates. The development of RPE cell-type conversions along the neural and mesenchymal pathways from the aspect of changes in the molecular genetic internal and external patterns occurs in different ways.…”