Ye Shan-Shan, Tang Yong, Song Jian-Tao
Eye Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
International Collaborative Centre on Big Science Plan for Purinergic Signalling, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2021 Jun 15;12:654445. doi: 10.3389/fphar.2021.654445. eCollection 2021.
Extracellular ATP and its ultimate degradation product adenosine are potent extracellular signaling molecules that elicit a variety of pathophysiological pathways in retina through the activation of P2 and P1 purinoceptors, respectively. Excessive build-up of extracellular ATP accelerates pathologic responses in retinal diseases, whereas accumulation of adenosine protects retinal cells against degeneration or inflammation. This mini-review focuses on the roles of ATP and adenosine in three types of blinding diseases including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR). Several agonists and antagonists of ATP receptors and adenosine receptors (ARs) have been developed for the potential treatment of glaucoma, DR and AMD: antagonists of P2X7 receptor (P2X7R) (BBG, MRS2540) prevent ATP-induced neuronal apoptosis in glaucoma, DR, and AMD; A1 receptor (A1R) agonists (INO-8875) lower intraocular pressure in glaucoma; A2A receptor (A2AR) agonists (CGS21680) or antagonists (SCH58261, ZM241385) reduce neuroinflammation in glaucoma, DR, and AMD; A3 receptor (A3R) agonists (2-Cl-lB-MECA, MRS3558) protect retinal ganglion cells (RGCs) from apoptosis in glaucoma.
细胞外ATP及其最终降解产物腺苷是有效的细胞外信号分子，分别通过激活P2和P1嘌呤受体在视网膜中引发多种病理生理途径。细胞外ATP的过度积累会加速视网膜疾病中的病理反应，而腺苷的积累则可保护视网膜细胞免于退化或炎症。本综述聚焦于ATP和腺苷在三种致盲性疾病中的作用，包括年龄相关性黄斑变性（AMD）、青光眼和糖尿病性视网膜病变（DR）。已经开发了几种ATP受体和腺苷受体（ARs）的激动剂和拮抗剂用于青光眼、DR和AMD的潜在治疗：P2X7受体（P2X7R）拮抗剂（BBG、MRS2540）可预防青光眼、DR和AMD中ATP诱导的神经元凋亡；A1受体（A1R）激动剂（INO-8875）可降低青光眼的眼压；A2A受体（A2AR）激动剂（CGS21680）或拮抗剂（SCH58261、ZM241385）可减轻青光眼、DR和AMD中的神经炎症；A3受体（A3R）激动剂（2-Cl-lB-MECA、MRS3558）可保护青光眼患者的视网膜神经节细胞（RGCs）免于凋亡。
