
Full text loading...
Our sense of sight relies on photoreceptors, which transduce photons into the nervous system's electrochemical interpretation of the visual world. These precious photoreceptors can be disrupted by disease, injury, and aging. Once photoreceptors start to die, but before blindness occurs, the remaining retinal circuitry can withstand, mask, or exacerbate the photoreceptor deficit and potentially be receptive to newfound therapies for vision restoration. To maximize the retina's receptivity to therapy, one must understand the conditions that influence the state of the remaining retina. In this review, we provide an overview of the retina's structure and function in health and disease. We analyze a collection of observations on photoreceptor disruption and generate a predictive model to identify parameters that influence the retina's response. Finally, we speculate on whether the retina, with its remarkable capacity to function over light levels spanning nine orders of magnitude, uses these same adaptational mechanisms to withstand and perhaps mask photoreceptor loss.
Article metrics loading...
Full text loading...
Literature Cited
Data & Media loading...
Download Supplemental Figures 1-4 (PDF). Download Supplemental Table 1: Related to Figures 2-4. Examples of findings following photoreceptor disruption. Comparison of studies on photoreceptor disruption to demonstrate how experimental design influences the results. Individual observations were assigned to one of three retinal outcomes (stability, degeneration, compensation). See Figure 2 for an explanation of these outcomes. Such a deconstruction of a study’s findings was done for each of the 151 original research studies used in the predictive model (Figures 3-4). Abbreviations: S1, sublamina 1 of the inner plexiform layer; AGB, cation 1-amino-4-guanidobutane used to probe permeation through ion channels. (PDF) Download Supplemental Table 2: Table of references and observations used for statistical modeling. Related to Figures 3 & 4. Table of references and observations, including the PMID of the studies; the assigned outcome (stability, degeneration, compensation); method of analysis (structure, function); timing of photoreceptor perturbation (development, maturity); photoreceptor type perturbed (rod, cone, both); biological process affected by the gene mutation (phototransduction, signaling, trafficking, other); age of photoreceptor disruption (in days and normalized by the age of retinal maturation in that species); interval between photoreceptor disruption and the observation time point (in days and normalized by the age of retinal maturation in that species); and the percent of photoreceptor loss; gene and mutant allele names causing photoreceptor loss. (XLSX)