Abstract
Purpose: :
Complement, dietary fat intake, and oxidant injury contribute to retinal pigment epithelial (RPE) cell damage and the accumulation of sub-retinal deposits in age-related macular degeneration (AMD). Membrane complement regulatory proteins (mCRPs) such as CD55 and CD59, protect cells from complement attack. In this study, we sought to investigate the impact of high-fat diet (HFD) and blue-green light (BL) exposure on the development of sub-RPE deposits and RPE injury in CD55/CD59 double deficient (KO) mice.
Methods: :
6-month old KO mice (HFD, n = 7) and age-matched C57BL/6 mice (WT) [HFD, n = 7; normal diet (ND), n = 5] were fed a HFD or ND for 6 months and the right eyes were exposed to non-phototoxic levels of BL over two weeks. The HFD was continued for 4 months. 4 months later, fundus examination was performed and serum cholesterol levels were determined. Eyes were processed for 1-µm-thick sections and stained with toluidine blue. 20 images centered at the optic nerve were captured using a 100x oil-immersion lens from each section for thick section light microscopic analysis of sub-RPE deposit and hypopigmentation severity (severity grading scale from 0-3).
Results: :
The plasma cholesterol levels in KO and WT mice fed a HFD were greater than those on a ND (P=0.04). No yellowish deposits were found by fundus examination in KO and WT mice. A significantly higher frequency of sub-RPE deposits was found in KO and WT mice fed a HFD exposed to BL (KOHL and WTHL, respectively) compared to WT mice fed a ND without BL exposure (WTN) [P<0.001; mean sub-RPE deposit grades in KOHL, WTHL and WTN were 1.4, 1.5, and 0.8, respectively]. The frequency of sub-RPE deposits did not differ in KOHL mice and WTHL mice (P>0.05). Furthermore, a significantly higher frequency of hypopigmentation was found in KOHL mice compared to WTHL mice and WTN mice (P<0.05; mean hypopigmentation grades in KOHL, WTHL and WTN were 1.6, 1.2, and 1.3, respectively). The frequency of hypopigmentation did not differ in WTHL mice and WTN mice (P>0.05).
Conclusions: :
Sub-RPE deposits developed in mice fed a HFD and treated with BL. The similarity of sub-RPE deposits in CD55/59 KO and WT mice under these conditions suggests that mCRPs other than, or in addition to CD55 and CD59 may help to protect RPE cells from complement and oxidant injury in diseases such as AMD. The higher frequency of hypopigmentation in CD55/59 KO mice on a HFD exposed to BL support an RPE cell protective role for CD55 and/or CD59 under these conditions.
Keywords: age-related macular degeneration • oxidation/oxidative or free radical damage • retinal pigment epithelium