濱田 健太郎さん

医学部医学科 2017年入学

2021年9月30日-10月1日 WEB開催

山梨大学薬理学講座教室所属 濱田健太郎





○濱田 健太郎1, 篠崎 陽一1,2, 壇上 洋右1, 久保田 友人1, 夏堀 晃世3, 齊藤 光像1,2, ビジェイ パラジュリ1,2, 繁冨 英治1, 柏木 賢治5, 田中 謙二4, 小泉 修一1,2 (1.山梨大学大学院総合研究部医学域薬理, 2.GLIA Center, Univ. Yamanashi, 3.Sleep disord. project, Tokyo Metr. Inst. Med. Sci., 4.Dept. Neuropsychiat., Keio Univ. Sch. Med., 5.Dept. Ophthalmol., Interdiscp. Grad. Sch. Med. Univ. Yamanashi)


Glaucoma is second leading cause of blindness worldwide, and is thought to be caused by degeneration of retinal ganglion cells (RGCs) due to an elevated intraocular pressure (IOP). In the last meeting, we reported that P2Y1 receptor is expressed in angle tissues and plays an essential role for IOP reduction. Thus P2Y1 receptor knockout (P2Y1KO) mice showed higher IOP and hypertensive glaucoma-like phenotype. However, P2Y1 receptor is also highly expressed in astrocyte-lineage cells in the retina.

To test the role of P2Y1 receptor in these cell types in physiological and pathophysiological functions in the retina, we selectively deleted P2Y1 receptor in astrocyte-linage cells using Mlc1-tTS::P2ry1tetO/tetO mice. We first investigate which cell type is regulated under control of Mlc1 promotor using Mlc1-tTA::YC-Cameleon-NanotetO/tetO, and found that the gene expression of Müller cells is selectively regulated by the Mlc-1-driver system. Next, we measured IOP of control and Müller cell-specific P2Y1 receptor conditional KO (MC-cKO) mice and found that MC-cKO mice showed no increase in IOP compared to control mice. However we found that MC-cKO mice showed significantly less number of RGCs (Rbpms-positive cells) than control mice at 12 months old (mo). In accordance with this, the number of apoptotic cells detected by TdT-mediated dUTP nick end labelling significantly increased in MC-cKO at 12 mo compared to age-matched control mice. Taken together, our results suggest that in addition to IOP control, P2Y1 receptor should play an important role in Müller cell function, and that its loss should cause RGC impairment in an IOP-independent mechanism.




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