Wang Meng, Yao Shi-Qi, Huang Yao, Liang Jia-Jian, Xu Yanxuan, Chen Shaowan, Wang Yuhang, Ng Tsz Kin, Chu Wai Kit, Cui Qi, Cen Ling-Ping
Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong; Shantou University Medical College, Shantou, Guangdong Province, China.
Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Neural Regen Res. 2024 May;19(5):1112-1118. doi: 10.4103/1673-5374.385310.
Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma, the leading cause of irreversible blindness. We previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve injury. To investigate the underlying mechanism, in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor (4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole) by intravitreal injection. We found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating macrophages. Transcriptomic analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 inhibitors. Furthermore, casein kinase-2 inhibition downregulated the expression of genes (Cck, Htrsa, Nef1, Htrlb, Prph, Chat, Slc18a3, Slc5a7, Scn1b, Crybb2, Tsga10ip, and Vstm21) involved in intraocular pressure elevation. Our data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.
眼压升高可导致视网膜神经节细胞死亡，是青光眼（不可逆性失明的主要原因）临床上可逆转的危险因素。我们之前证明，酪蛋白激酶2抑制可促进视神经损伤后大鼠视网膜神经节细胞存活和轴突再生。为了研究潜在机制，在本研究中，我们将成年大鼠眼压升高至75 mmHg持续2小时，然后通过玻璃体内注射给予酪蛋白激酶2抑制剂（4,5,6,7-四溴-2-氮杂苯并咪唑或2-二甲基氨基-4,5,6,7-四溴-1H-苯并咪唑）。我们发现，玻璃体内注射4,5,6,7-四溴-2-氮杂苯并咪唑或2-二甲基氨基-4,5,6,7-四溴-1H-苯并咪唑可促进视网膜神经节细胞存活并减少浸润巨噬细胞数量。转录组分析表明，丝裂原活化蛋白激酶信号通路参与了对眼压升高的反应，但不受酪蛋白激酶2抑制剂的调节。此外，酪蛋白激酶2抑制下调了与眼压升高相关的基因（Cck、Htrsa、Nef1、Htrlb、Prph、Chat、Slc18a3、Slc5a7、Scn1b、Crybb2、Tsga10ip和Vstm21）的表达。我们的数据表明，抑制酪蛋白激酶2可通过使巨噬细胞失活来提高急性眼压升高后大鼠视网膜神经节细胞的存活率。
