Abstract

Volume.122 Number.3

A Ray of Hope from Genetics
Motokazu Tsujikawa
Department of Visual Regenerative Medicine, Osaka University Graduate School of Medicine

Diseases are a caused by genetic and environmental factors. Because genetic factors cannot be manipulated, except in rare cases, we intervene with environmental factors for preventing and treating diseases. In this review, I describe several diseases in which environmental factors are also controlled by genetic factors. Gelatinous drop-like corneal dystrophy is a severe corneal disease that is commonly observed in Japanese individuals. We have successfully identified the responsible gene for this Mendelian disease TACSTD. We demonstrated that the function of TACSTD2 is related to the stability of claudins (CLDN), which play an important role in corneal epithelial barrier function, and obtained pathogenesis of several clinical findings and supporting evidence for the effectiveness of treatment with contact lens. Environmental factors also affect the progression of Mendelian disease, but these environmental factors are controlled by genetic factors. Retinitis pigmentosa is a common retinal disease. To date, >80 responsible genes have been identified. Many patients have two major questions. These are regarding the risk of passing it onto their family and children, in particular, and the question of whether light, which is an environmental factor, may worsen the disease. Because retinitis pigmentosa is a late progressive disease, rather than simply determining its genotype, it is necessary to evaluate using the age-onset curve. For evaluation in terms of light, we used several disease models to demonstrate that ectopic phototransduction is a key mechanism for light causing photoreceptor cell death via adenylyl cyclase activation. Cell death by an important environmental factor, light, is also controlled by a genetic pathway. The identification of these genetic factors is important for understanding the underlying disease mechanism and developing new therapies.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 122: 180-199, 2018.

Key words
Genetics, Gelatinous drop-like corneal dystrophy, Retinitis pigmentosa, Age-related macular degeneration, Zebrafish
Reprint requests to
Motokazu Tsujikawa, M.D., Ph.D. Department of Visual Regenerative Medicine, Osaka University Graduate School of Medicine. 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan