PMID- 32355441 OWN - NLM STAT- MEDLINE DCOM- 20210510 LR - 20211204 IS - 1090-0535 (Electronic) IS - 1090-0535 (Linking) VI - 26 DP - 2020 TI - Effect of vitamin B(12) supplementation on retinal lesions in diabetic rats. PG - 311-325 AB - PURPOSE: Diabetic retinopathy (DR) is the most common complication of diabetes involving microvasculature and neuronal alterations in the retina. Previously, we reported that vitamin B(12) deficiency could be an independent risk factor for DR in humans. However, the effect of vitamin B(12) supplementation in experimental DR is unknown. Thus, in this study, we investigated the impact of dietary supplementation of vitamin B(12) on retinal changes in diabetic rats. METHODS: Diabetes was induced in 2-month-old Sprague-Dawley rats and maintained for 4 months. One group of diabetic rats were fed normal levels of vitamin B(12), and one group double the quantity of vitamin B(12) (50 microg/kg diet). Vitamin B(12) and homocysteine levels in the plasma were analyzed with radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC), respectively. At the end of 4 months of experimentation, the eyeballs were collected. Retinal changes were analyzed with hematoxylin and eosin (H&E) staining, immunoblotting, and immunofluorescence methods. RESULTS: Dietary supplementation of vitamin B(12) had no effect on food intake, bodyweight, fasting blood glucose, and plasma homocysteine levels in the diabetic rats. However, vitamin B(12) supplementation prevented loss of rhodopsin, and overexpression of VEGF, and completely prevented overexpression of HIF1alpha, GFAP, and endoplasmic reticulum (ER) stress markers (GRP78, ATF6alpha, XBP1, CHOP, and caspase 12) in the diabetic rat retina. Further, vitamin B(12) ameliorated apoptosis in the retina as shown with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and prevented retinal thinning. CONCLUSIONS: Vitamin B(12) supplementation of diabetic rats appeared to be beneficial by circumventing retinal hypoxia, VEGF overexpression, and ER stress-mediated cell death in the retina. The present study adds another potential therapeutic strategy of vitamin B(12) in diabetes. CI - Copyright (c) 2020 Molecular Vision. FAU - Reddy, S Sreenivasa AU - Reddy SS AD - Biochemistry Division, National Institute of Nutrition, Hyderabad, India. FAU - Prabhakar, Y K AU - Prabhakar YK AD - Biochemistry Division, National Institute of Nutrition, Hyderabad, India. FAU - Kumar, Ch Uday AU - Kumar CU AD - Biochemistry Division, National Institute of Nutrition, Hyderabad, India. FAU - Reddy, P Yadagiri AU - Reddy PY AD - Biochemistry Division, National Institute of Nutrition, Hyderabad, India. FAU - Reddy, G Bhanuprakash AU - Reddy GB AD - Biochemistry Division, National Institute of Nutrition, Hyderabad, India. LA - eng PT - Journal Article DEP - 20200424 PL - United States TA - Mol Vis JT - Molecular vision JID - 9605351 RN - 0 (Activating Transcription Factor 6) RN - 0 (Atf6 protein, rat) RN - 0 (Blood Glucose) RN - 0 (Ddit3 protein, rat) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (GFAP protein, rat) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (HSPA5 protein, human) RN - 0 (Heat-Shock Proteins) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (X-Box Binding Protein 1) RN - 0 (Xbp1 protein, rat) RN - 0LVT1QZ0BA (Homocysteine) RN - 147336-12-7 (Transcription Factor CHOP) RN - 9009-81-8 (Rhodopsin) RN - EC 3.4.22.- (Caspase 12) RN - P6YC3EG204 (Vitamin B 12) SB - IM MH - Activating Transcription Factor 6/blood MH - Animals MH - Apoptosis/*drug effects/physiology MH - Blood Glucose/drug effects MH - Body Weight/drug effects MH - Caspase 12/blood MH - Chromatography, High Pressure Liquid MH - Diabetes Mellitus, Experimental/*blood/drug therapy/metabolism MH - Diabetic Retinopathy/*blood/*diet therapy MH - Endoplasmic Reticulum Chaperone BiP MH - Endoplasmic Reticulum Stress/*drug effects/physiology MH - Glial Fibrillary Acidic Protein/blood MH - Heat-Shock Proteins/blood MH - Homocysteine/blood MH - Hypoxia-Inducible Factor 1, alpha Subunit/blood MH - Immunohistochemistry MH - Male MH - Radioimmunoassay MH - Rats MH - Rats, Sprague-Dawley MH - Rhodopsin/blood MH - Transcription Factor CHOP/blood MH - Vascular Endothelial Growth Factor A/blood MH - Vitamin B 12/*administration & dosage/blood MH - X-Box Binding Protein 1/blood PMC - PMC7190579 EDAT- 2020/05/02 06:00 MHDA- 2021/05/11 06:00 PMCR- 2020/01/01 CRDT- 2020/05/02 06:00 PHST- 2020/01/09 00:00 [received] PHST- 2020/04/22 00:00 [accepted] PHST- 2020/05/02 06:00 [entrez] PHST- 2020/05/02 06:00 [pubmed] PHST- 2021/05/11 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 26 [pii] PST - epublish SO - Mol Vis. 2020 Apr 24;26:311-325. eCollection 2020.