Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (5): 1112-1118.doi: 10.4103/1673-5374.385310

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Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

Meng Wang1, 2, Shi-Qi Yao1, 2, Yao Huang3, Jia-Jian Liang1, Yanxuan Xu1, Shaowan Chen1, Yuhang Wang1, Tsz Kin Ng1, 2, 4, #br# Wai Kit Chu4, Qi Cui1, 4, Ling-Ping Cen1, 2, *#br#   

  1. 1Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou, Guangdong Province, China; 2Shantou University Medical College, Shantou, Guangdong Province, China; 3Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China; 4Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
  • Online:2024-05-15 Published:2023-10-31
  • Contact: Ling-Ping Cen, MD, PhD, cenlp@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81570849, 81100931; the Natural Science Foundation of Guangdong Province of China, Nos. 2015A030313446, 2020A1515011413 (all to LPC).

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Abstract: 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-1H-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. 

Key words: casein kinase-2, glaucoma, intraocular pressure elevation, macrophages, retinal ganglion cells