Retinal remodeling

Abstract

Retinal photoreceptor degeneration takes many forms. Mutations in rhodopsin genes or disorders of the retinal pigment epithelium, defects in the adenosine triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine kinase defects, ciliopathies and transport defects, defects in both transducin and arrestin, defects in rod cyclic guanosine 3′,5′-monophosphate phosphodiesterase, peripherin defects, defects in metabotropic glutamate receptors, synthetic enzymatic defects, defects in genes associated with signaling, and many more can all result in retinal degenerative disease like retinitis pigmentosa (RP) or RP-like disorders. Age-related macular degeneration (AMD) and AMD-like disorders are possibly due to a constellation of potential gene targets and gene/gene interactions, while other defects result in diabetic retinopathy or glaucoma. However, all of these insults as well as traumatic insults to the retina result in retinal remodeling. Retinal remodeling is a universal finding subsequent to retinal degenerative disease that results in deafferentation of the neural retina from photoreceptor input as downstream neuronal elements respond to loss of input with negative plasticity. This negative plasticity is not passive in the face of photoreceptor degeneration, with a phased revision of retinal structure and function found at the molecular, synaptic, cell, and tissue levels involving all cell classes in the retina, including neurons and glia. Retinal remodeling has direct implications for the rescue of vision loss through bionic or biological approaches, as circuit revision in the retina corrupts any potential surrogate photoreceptor input to a remnant neural retina. However, there are a number of potential opportunities for intervention that are revealed through the study of retinal remodeling, including therapies that are designed to slow down photoreceptor loss, interventions that are designed to limit or arrest remodeling events, and oplogenetic approaches that target appropriate classes of neurons in the remnant neural retina.

Development of a Chromatic Pupillography Protocol for the First Gene Therapy Trial in Patients With CNGA3-Linked Achromatopsia

“…Reorganization of the retinal architecture as a consequence of retinal dysfunction and/or degeneration has been described by other authors in a number of photoreceptor retinal disorders. 29,30 This hypothesis is supported by the finding of ectopic synapses between rods and cone bipolar cells in the Cnga3…”

Outer Segment Thickness Predicts Visual Field Response to QLT091001 in Patients withRPE65orLRATMutations

“…The improvement of GVF in responders suggests that, although significant photoreceptor degeneration occurs in LCA and RP, the bipolar cells and proximal visual system still effectively receive synaptic inputs from the surviving photoreceptors, despite neural remodeling found in degenerating retina. [23][24][25][26][27][28] Thus, significant and sustained visual function improvements were shown with QLT091001.…”

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

“…Early aberrant neurite sprouting in the glycinergic and GABAergic amacrine cell populations have been found in a porcine animal model of RP in the early stages of degeneration. Finally, remodeling events in both glycinergic and GABAergic amacrine cells in human geographic atrophy, with aberrant sprouting in both cell signals, have also been described (Jones et al, 2012).…”