TY - JOUR
T1 - Glial, Neuronal, Vascular, Retinal Pigment Epithelium, and Inflammatory Cell Damage in a New Western Diet–Induced Primate Model of Diabetic Retinopathy
AU - Chan-Ling, Tailoi
AU - Hu, Ping
AU - Calzi, Sergio
AU - Warner, Jeff
AU - Uddin, Nasir
AU - DuPont, Mariana
AU - Neuringer, Martha
AU - Kievit, Paul
AU - Renner, Lauren
AU - Stoddard, Jonathan
AU - Ryals, Renee
AU - Boulton, Michael
AU - McGill, Trevor
AU - Grant, Maria
N1 - Funding Information:
Supported by Research to Prevent Blindness (unrestricted departmental funds; M.B.G.); Vision Science Research Center core grant P30 EY003039 (M.B.G.); NIH grants R01EY032753, R01EY025383, R01EY028858, R01EY012601, R01EY028037, EY012601, EY007739, EY025383, EY028858, and HL110170 (M.B.G.); National Health and Medical Research Council Principal Research Fellowship 1005730 (T.C.-L.); Baxter Charitable Foundation grant (T.C.-L.); The Ronald Geoffrey Arnott Foundation grant (T.C.-L.); National Primate Research Center grant P51 OD011092 (M.N.); and Oregon National Primate Research Center Core grant (M.N.).
Funding Information:
Supported by Research to Prevent Blindness (unrestricted departmental funds; M.B.G.); Vision Science Research Center core grant P30 EY003039 (M.B.G.); NIH grants R01EY032753 , R01EY025383 , R01EY028858 , R01EY012601 , R01EY028037 , EY012601 , EY007739 , EY025383 , EY028858 , and HL110170 (M.B.G.); National Health and Medical Research Council Principal Research Fellowship 1005730 (T.C.-L.); Baxter Charitable Foundation grant (T.C.-L.); The Ronald Geoffrey Arnott Foundation grant (T.C.-L.); National Primate Research Center grant P51 OD011092 (M.N.); and Oregon National Primate Research Center Core grant (M.N.).
Publisher Copyright:
© 2023 American Society for Investigative Pathology
PY - 2023/11
Y1 - 2023/11
N2 - This study investigated retinal changes in a Western diet (WD)–induced nonhuman primate model of type 2 diabetes. Rhesus nonhuman primates, aged 15 to 17 years, were fed a high-fat diet (n = 7) for >5 years reflective of the traditional WD. Age-matched controls (n = 6) were fed a standard laboratory primate diet. Retinal fundus photography, optical coherence tomography, autofluorescence imaging, and fluorescein angiography were performed before euthanasia. To assess diabetic retinopathy (DR), eyes were examined using trypsin digests, lipofuscin autofluorescence, and multimarker immunofluorescence on cross-sections and whole mounts. Retinal imaging showed venous engorgement and tortuosity, aneurysms, macular exudates, dot and blot hemorrhages, and a marked increase in fundus autofluorescence. Post-mortem changes included the following: decreased CD31 blood vessel density (P < 0.05); increased acellular capillaries (P < 0.05); increased density of ionized calcium-binding adaptor molecule expressing amoeboid microglia/macrophage; loss of regular distribution in stratum and spacing typical of ramified microglia; and increased immunoreactivity of aquaporin 4 and glial fibrillary acidic protein (P < 0.05). However, rhodopsin immunoreactivity (P < 0.05) in rods and neuronal nuclei antibody–positive neuronal density of 50% (P < 0.05) were decreased. This is the first report of a primate model of DR solely induced by a WD that replicates key features of human DR.
AB - This study investigated retinal changes in a Western diet (WD)–induced nonhuman primate model of type 2 diabetes. Rhesus nonhuman primates, aged 15 to 17 years, were fed a high-fat diet (n = 7) for >5 years reflective of the traditional WD. Age-matched controls (n = 6) were fed a standard laboratory primate diet. Retinal fundus photography, optical coherence tomography, autofluorescence imaging, and fluorescein angiography were performed before euthanasia. To assess diabetic retinopathy (DR), eyes were examined using trypsin digests, lipofuscin autofluorescence, and multimarker immunofluorescence on cross-sections and whole mounts. Retinal imaging showed venous engorgement and tortuosity, aneurysms, macular exudates, dot and blot hemorrhages, and a marked increase in fundus autofluorescence. Post-mortem changes included the following: decreased CD31 blood vessel density (P < 0.05); increased acellular capillaries (P < 0.05); increased density of ionized calcium-binding adaptor molecule expressing amoeboid microglia/macrophage; loss of regular distribution in stratum and spacing typical of ramified microglia; and increased immunoreactivity of aquaporin 4 and glial fibrillary acidic protein (P < 0.05). However, rhodopsin immunoreactivity (P < 0.05) in rods and neuronal nuclei antibody–positive neuronal density of 50% (P < 0.05) were decreased. This is the first report of a primate model of DR solely induced by a WD that replicates key features of human DR.
UR - http://www.scopus.com/inward/record.url?scp=85160045275&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ajpath.2023.02.019
DO - https://doi.org/10.1016/j.ajpath.2023.02.019
M3 - Article
SN - 1525-2191
VL - 193
SP - 1789
EP - 1808
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 11
ER -