Retinal Ganglion Cell Loss and Mild Vasculopathy in Methylene Tetrahydrofolate Reductase (Mthfr)-Deficient Mice: A Model of Mild Hyperhomocysteinemia

Investigative Ophthalmology & Visual Science
Shanu MarkandSylvia B Smith

Abstract

Methylenetetrahydrofolate reductase (Mthfr) is a key enzyme in homocysteine-methionine metabolism. We investigated Mthfr expression in retina and asked whether mild hyperhomocysteinemia, due to Mthfr deficiency, alters retinal neurovascular structure and function. Expression of Mthfr was investigated at the gene and protein level using quantitative (q) RT-PCR, in situ hybridization, immunoblotting, and immunohistochemistry (IHC). The Mthfr+/+ and Mthfr+/- mice were subjected to comprehensive evaluation using ERG, funduscopy, fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), HPLC, and morphometric and IHC analysis of glial fibrillary acidic protein (GFAP) at 8 to 24 weeks. Gene and protein analyses disclosed widespread retinal expression of Mthfr. Electroretinography (ERG) revealed a significant decrease in positive scotopic threshold response in retinas of Mthfr+/- mice at 24 weeks. Fundus examination in mice from both groups was normal; FA revealed areas of focal vascular leakage in 20% of Mthfr+/- mice at 12 to 16 weeks and 60% by 24 weeks. The SD-OCT revealed a significant decrease in nerve fiber layer (NFL) thickness at 24 weeks in Mthfr+/- compared to Mthfr+/+ mice. There was a 2-fold ele...Continue Reading

Citations

Jun 15, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jing WangSylvia B Smith
Mar 30, 2017·Documenta Ophthalmologica. Advances in Ophthalmology·Alan B SaulSylvia B Smith
Dec 20, 2019·Scientific Reports·Mariam Lofty KhaledYutao Liu
Dec 17, 2016·Journal of Cellular Biochemistry·Avisek MajumderSuresh C Tyagi
Jan 1, 2021·Toxicologic Pathology·Anantharaman MuthuswamyOlulanu H Aina
Aug 19, 2015·Experimental Eye Research·Adam Hedberg-BuenzMichael G Anderson
Jun 19, 2021·Photodiagnosis and Photodynamic Therapy·Hatice Kubra SonmezGuzel Erkan

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