Photoreceptor degeneration and loss of retinal function in the C57BL/6-C(2J) mouse
Date
2004
Authors
Bravo-Nuevo, A
Walsh, Natalie
Stone, Jonathan
Journal Title
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Volume Title
Publisher
Association for Research in Vision and Opthalmology
Abstract
PURPOSE. The C57BL/6-c2J (c2J) mouse strain has been shown in earlier studies to be highly resistant to light damage. Subsequent studies related this resistance to an amino acid substitution (leu450met) in a pigment epithelial enzyme (RPE65), which slowed the rate of rhodopsin regeneration. The present study was conducted to examine patterns of photoreceptor death, electrophysiological function (the ERG) and trophic factor expression over the life of the C57BL/6-c2J retina. METHODS. Observations were made on two C57BL/6J-c2J substrains, one albino (Tyr/Tyr) and one pigmented (Tyr/+), and two nondegenerative strains, one albino (BALB/cJ) and one pigmented (C57BL/6J). Mice were raised in dim cyclic light (12 hours at 5 lux, 12 hours in the dark), and a developmental series of retinas of each strain was taken between postnatal day (P)4 and (P365+). Retinas were examined for cell death by using the TUNEL technique, stress-induced protein expression (FGF-2 and GFAP), and measures of retinal thickness. The dark-adapted ERG was recorded in dark-adapted conditions in early adulthood (13-15 weeks) and late adulthood (>1 year). RESULTS. In both C57BL/6-c2J substrains, the retina showed marked degenerative features when compared with two control strains, BALB/cJ (leucine at codon 450 in RPE65) and C57BL/6J (methionine). During development and into young adulthood, photoreceptor death rates were abnormally high, levels of two stress-inducible proteins (FGF-2 and GFAP) were abnormally high, and the ERG (electroretinogram) was significantly reduced in amplitude (<50% of values in BALB/cJ or C57BL/6J). The rate of photoreceptor death remained abnormally high into young adulthood (2-3 months) but decreased to control levels by 1 year. Accordingly, the thickness of the outer nuclear layer and the ERG were stable over the same period. CONCLUSIONS. Results suggest that a still-unidentified stress increases photoreceptor death in the C57BL/6-c2J retina during the critical period of photoreceptor development and into young adulthood, upregulates stress-inducible factors, and markedly limits the amplitude of the ERG, These degenerative changes do not continue after early adulthood, the retina remaining stable in structure and function into late adulthood. The degenerative changes were apparent in both albino and pigmented C57BL/6-c2J substrains. Their genetic cause remains unknown.
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Keywords
Keywords: DNA; fibroblast growth factor 2; glial fibrillary acidic protein; leucine; methionine; rhodopsin; fibroblast growth factor 2; glial fibrillary acidic protein; animal experiment; animal model; animal tissue; article; cell death; cell survival; controlled s
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Source
Investigative Ophthalmology and Visual Science
Type
Journal article