Bietti's crystalline dystrophy (BCD) is a heredita ry retinal degenerative disease with high prevalence among Japanese, and it is reported to be caused by mutations in CYP4V2, a member of the hydroxylase cytochrome P450 family. In patients with BCD, retinal pigment epithelium and photoreceptor cells dege nerate, thus eventually leading to blindness. While there is considerable requirement to elucidate the pathological condition and therapeutic methods, elu ci dation remains difficult because it has been impossible to collect diseased cells from a patient. Using comprehensive lipid analysis on retinal pigment epithelium cells differentiated from patient-derived iPS cells, we demonstrated that free cholesterol accumulation causes cellular degeneration. Furthermore, it was possible to inhibit the cellular degeneration of patient-derived retinal pigment epithelium cells by ameliorating free cholesterol accumulation with cyclodextrin derivatives. We believe that as a result of novel elucidation of the pathogenesis mechanism, progress in drug discovery research for intractable diseases for which there are no therapeutic agents can be expected.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 124: 896-901, 2020.