RT Journal Article
SR Electronic
T1 Temporal Contrast Sensitivity Increases Despite Photoreceptor Degeneration in a Mouse Model of Retinitis Pigmentosa
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0020-21.2021
DO 10.1523/ENEURO.0020-21.2021
A1 Rose L. Pasquale
A1 Ying Guo
A1 Yumiko Umino
A1 Barry Knox
A1 Eduardo Solessio
YR 2021
UL http://www.eneuro.org/content/early/2021/01/26/ENEURO.0020-21.2021.abstract
AB The detection of temporal variations in amplitude of light intensity, or temporal contrast sensitivity (TCS), depends on the kinetics of rod photoresponse recovery. Uncharacteristically fast rod recovery kinetics are facets of both human patients and transgenic animal models with a P23H rhodopsin mutation, a prevalent cause of retinitis pigmentosa. Here, we show that mice with this mutation (RhoP23H/+) exhibit an age- and illumination-dependent enhancement in TCS compared to controls. At retinal illumination levels producing ≥1000 R*/rod/s or more, P30 RhoP23H/+ mice exhibit a 1.2 to 2-fold increase in retinal and optomotor TCS relative to controls in response to flicker frequencies of 3, 6, and 12 Hz despite significant photoreceptor degeneration and loss of flash ERG b-wave amplitude. Surprisingly, the TCS of RhoP23H/+ mice further increases as degeneration advances. Enhanced TCS is also observed in a second model (rhodopsin heterozygous mice, Rho+/-) with fast rod recovery kinetics and no apparent retinal degeneration. In both mouse models, enhanced TCS is explained quantitatively by a comprehensive model that includes photoresponse recovery kinetics, density and collecting area of degenerating rods. Measurement of TCS may be a non-invasive early diagnostic tool indicative of rod dysfunction in some forms of retinal degenerative disease.Significance Statement Retinal degeneration in humans causes loss of retinal cells, loss of retinal function, and eventual blindness. Understanding the retinal and visual changes that occur early in retinal degenerative disease is critical for improving therapeutic strategies and treatment outcomes. We show here an enhanced ability to detect flickering lights that develops during early retinal degeneration in a mouse model of a human disease. This surprising gain-of-function was caused by a pathological acceleration of the temporal properties of rod photoresponses. In humans, advanced rod dysfunction is currently diagnosed using full-field ERG and perimetry. Measurement of retinal or visual sensitivity to flickering lights such as used here could prove useful as a rapid test for early rod dysfunction in retinal degeneration.