TY - JOUR
T1 - Light deprivation reduces the severity of experimental diabetic retinopathy
AU - Thebeau, Christina
AU - Zhang, Sheng
AU - Kolesnikov, Alexander V.
AU - Kefalov, Vladimir J.
AU - Semenkovich, Clay F.
AU - Rajagopal, Rithwick
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/4
Y1 - 2020/4
N2 - Illumination of the retina is a major determinant of energy expenditure by its neurons. However, it remains unclear whether light exposure significantly contributes to the pathophysiology of common retinal disease. Driven by the premise that light exposure reduces the metabolic demand of the retina, recent clinical trials failed to demonstrate a benefit for constant illumination in the treatment of diabetic retinopathy. Here, we instead ask whether light deprivation or blockade of visual transduction could modulate the severity of this common cause of blindness. We randomized adult mice with two different models of diabetic retinopathy to 1-3 months of complete dark housing. Unexpectedly, we find that diabetic mice exposed to short or prolonged light deprivation have reduced diabetes-induced retinal pathology, using measures of visual function, compared to control animals in standard lighting conditions. To corroborate these results, we performed assays of retinal vascular health in diabetic Gnat1−/− and Rpe65−/− mice, which lack phototransduction. Both mutants displayed less diabetes-associated retinal vascular disease compared to respective wild-type controls. Collectively, these results suggest that light-induced visual transduction promotes the development of diabetic retinopathy and implicate photoreceptors as an early source of visual pathology in diabetes.
AB - Illumination of the retina is a major determinant of energy expenditure by its neurons. However, it remains unclear whether light exposure significantly contributes to the pathophysiology of common retinal disease. Driven by the premise that light exposure reduces the metabolic demand of the retina, recent clinical trials failed to demonstrate a benefit for constant illumination in the treatment of diabetic retinopathy. Here, we instead ask whether light deprivation or blockade of visual transduction could modulate the severity of this common cause of blindness. We randomized adult mice with two different models of diabetic retinopathy to 1-3 months of complete dark housing. Unexpectedly, we find that diabetic mice exposed to short or prolonged light deprivation have reduced diabetes-induced retinal pathology, using measures of visual function, compared to control animals in standard lighting conditions. To corroborate these results, we performed assays of retinal vascular health in diabetic Gnat1−/− and Rpe65−/− mice, which lack phototransduction. Both mutants displayed less diabetes-associated retinal vascular disease compared to respective wild-type controls. Collectively, these results suggest that light-induced visual transduction promotes the development of diabetic retinopathy and implicate photoreceptors as an early source of visual pathology in diabetes.
KW - Db/db
KW - Diabetic retinopathy
KW - Electroretinography
KW - Gnat1
KW - Light deprivation
KW - Rpe65
KW - Streptozotocin
KW - transducin1
UR - http://www.scopus.com/inward/record.url?scp=85078826198&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2020.104754
DO - 10.1016/j.nbd.2020.104754
M3 - Article
C2 - 31978605
AN - SCOPUS:85078826198
SN - 0969-9961
VL - 137
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 104754
ER -