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Hua Yang, Ming Yuan, Patel Gaurang, Aixu Sun, Adrianna Latuszek, Ying Hu, Jingtai Cao, Carl Romano; Differential expression of complement genes in mammalian eyes. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4594 – F0386.
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© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) results from a complex interaction of environmental and genetic risk factors. Genetic studies have shown complement genes are strongly associated with AMD. Rodent models based on expression of human genetic risk variants in complement genes have exhibited only limited phenotypic similarity to human disease. In the present study we have compared complement Factor H (CFH) and complement component 3 (C3) mRNA expression in different species eye (e.g. mouse, rat and human).
Paraffin sections or cryosections of mouse, rat and normal human donor eyes were used for in situ hybridization assay to determine the CFH and C3 expression. Manufacturer’s (Advanced Cell Diagnostics) instructions were followed for RNAscope® experiments. CFH and C3probes for different species were applied. Negative controls, e.g. DapB and positive probes or tissues (Liver), were included.
In rodent eye (both rat and mouse), CFH mRNA is strongly expressed in the retinal pigment epithelium with some expression also found in inner nuclear (INL) and retinal ganglion cell (RGC) layers of the retina. C3 mRNA is expressed mainly in RGC, INL of retina, ciliary body, corneal epithelium with some expression is also found in rodent retinal pigment epithelium layer. However, in human eye, CFH and C3 mRNA are strongly expressed in the choroid. Some expression is also found in RGC, INL layer of retina, ONH, sclera, cornea endothelial and stroma; andciliary body. There is no C3 or CFH signal detected in RPE cells.
The complement genes are present in ocular tissues, where they could play an important role in the pathogeneses of age-related macular degeneration. Our results show that complement factor H and C3 expression localization are quite different between human and rodent eyes. Rodent animal models based on manipulating CFH or C3 expression might not represent human disease because of these anatomic differences.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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