TY - JOUR
T1 - NAD + and sirtuins in retinal degenerative diseases
T2 - A look at future therapies
AU - Lin, Jonathan B.
AU - Apte, Rajendra S.
N1 - Funding Information:
This work was supported by the National Institutes of Health ( R01 EY019287 , P30 EY02687 , T32 GM07200 , UL1 TR002345 , TL1 TR002344 ); the Starr Foundation (R.S.A.); the Carl Marshall Reeves and Mildred Almen Reeves Foundation (R.S.A.); the Bill and Emily Kuzma Family Gift for retinal research (R.S.A.); Research to Prevent Blindness (R.S.A.); the Jeffrey Fort Innovation Fund (R.S.A.); the Glenn Foundation (R.S.A.); and the Thome Foundation (R.S.A.). Additional funding comes from an unrestricted grant to the Department of Ophthalmology and Visual Sciences of Washington University School of Medicine from Research to Prevent Blindness. R.S.A. is a co-founder of Metro International, which is developing NMN-based therapeutics. The authors would like to thank Andrea Santeford and Teresa Chen for technical assistance and Danyel Cavazos for help with scientific illustrations.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/11
Y1 - 2018/11
N2 - Retinal degenerative diseases are a major cause of morbidity in modern society because visual impairment significantly decreases the quality of life of patients. A significant challenge in treating retinal degenerative diseases is their genetic and phenotypic heterogeneity. However, despite this diversity, many of these diseases share a common endpoint involving death of light-sensitive photoreceptors. Identifying common pathogenic mechanisms that contribute to photoreceptor death in these diverse diseases may lead to a unifying therapy for multiple retinal diseases that would be highly innovative and address a great clinical need. Because the retina and photoreceptors, in particular, have immense metabolic and energetic requirements, many investigators have hypothesized that metabolic dysfunction may be a common link unifying various retinal degenerative diseases. Here, we discuss a new area of research examining the role of NAD + and sirtuins in regulating retinal metabolism and in the pathogenesis of retinal degenerative diseases. Indeed, the results of numerous studies suggest that NAD + intermediates or small molecules that modulate sirtuin function could enhance retinal metabolism, reduce photoreceptor death, and improve vision. Although further research is necessary to translate these findings to the bedside, they have strong potential to truly transform the standard of care for patients with retinal degenerative diseases.
AB - Retinal degenerative diseases are a major cause of morbidity in modern society because visual impairment significantly decreases the quality of life of patients. A significant challenge in treating retinal degenerative diseases is their genetic and phenotypic heterogeneity. However, despite this diversity, many of these diseases share a common endpoint involving death of light-sensitive photoreceptors. Identifying common pathogenic mechanisms that contribute to photoreceptor death in these diverse diseases may lead to a unifying therapy for multiple retinal diseases that would be highly innovative and address a great clinical need. Because the retina and photoreceptors, in particular, have immense metabolic and energetic requirements, many investigators have hypothesized that metabolic dysfunction may be a common link unifying various retinal degenerative diseases. Here, we discuss a new area of research examining the role of NAD + and sirtuins in regulating retinal metabolism and in the pathogenesis of retinal degenerative diseases. Indeed, the results of numerous studies suggest that NAD + intermediates or small molecules that modulate sirtuin function could enhance retinal metabolism, reduce photoreceptor death, and improve vision. Although further research is necessary to translate these findings to the bedside, they have strong potential to truly transform the standard of care for patients with retinal degenerative diseases.
KW - Metabolism
KW - Mitochondria
KW - NAD
KW - Neurodegeneration
KW - Retinal degeneration
KW - Sirtuins
UR - http://www.scopus.com/inward/record.url?scp=85048563271&partnerID=8YFLogxK
U2 - 10.1016/j.preteyeres.2018.06.002
DO - 10.1016/j.preteyeres.2018.06.002
M3 - Review article
C2 - 29906612
AN - SCOPUS:85048563271
SN - 1350-9462
VL - 67
SP - 118
EP - 129
JO - Progress in Retinal and Eye Research
JF - Progress in Retinal and Eye Research
ER -