Non-histone nuclear protein play important roles for photoreceptor function and experimental choroidal neovascularization

Abstract

Purpose : We reported an important role of a non-nuclear protein, high-mobility group protein N1 (HMGN1) that enhances endothelial growth factor (VEGF) in retinal pigment epithelium (RPE). We planned to examine the retinal function using genetically modified mice model and various age of normal control mice.

Methods : HMGN1 knockout mice, HMGN1^tm1/tm1 was used in this study. Electroretinogram (ERG), optical coherence tomography (OCT), and histological examination (HE) as well as routine ophthalmological examinations were performed in young and old mice. These mice were also used for laser-induced choroidal neovascular (CNV) experiments and evaluated by fluorescein angiography (FA), flat mount, histological examinations and gene expressions.

Results : Statistically significant less amplitude of cone a and b waves were observed on ERG in HMGN1^tm1/tm1 mice if compared to those of normal control. The tendency was clearer when we examined older HMGN1^tm1/tm1 mice. HE showed significant less outer nuclear layer thickness at some points. Statistically significant less VEGF expression was observed in RPE/choroid/sclera of HMGN1^tm1/tm1 when we made CNV. Statistically significant decrease of the size of laser-induced CNV was also observed in the HMGN1^tm1/tm1 mice when compared to those of age-matched control mice in both FA and measurement of flat mount CNV areas.

Conclusions : HMGN1 may play important roles in some of the physiological and/or pathological conditions, such as cone function and CNV generation.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.