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AIM: To investigate the neuroprotection of lomerizine(LOM)on retinal ganglion cells(RGCs)in early diabetic rats and their mechanism.<p>METHODS: Adult male Spraque - Dawley(SD)rats were randomly divided into control(CON), diabetes mellitus(DM), lomerizine(LOM)group, and each group had 40 rats. Diabetes rat model was induced by Streptozotocin(STZ)of intraperitoneal injection of 60 mg/kg of disposable. In LOM group, after model was established, rats were lavaged LOM by the dosage of 60mg/kg daily, the CON group and DM group were given the same dosage sodium chloride. In 4^th, 8^th, 12^th wk, RGCs' apoptosis were detected by HE, TUNEL, transmission electron microscope, and TUNEL and laser confocal microscope detection was used to test the calcium ion concentration.<p>RESULTS: Morphological observation: with the extension of the DM, RGCs decreased gradually and appeared disordered arrangement of cells. In DM group, different stages of apoptosis were observed by transmission electron microscope and got worse gradually with its extension. In LOM group, compared with DM group in the same period, RGCs apoptosis signs diminished gradually at 8^th and 12^th wk. TUNEL detection: no apoptotic RGCs was observed in CON group. In DM group, few TUNEL positive RGCs were seen at 4^th wk, and became more and more gradually. The apoptosis index was significantly higher in DM group compared with CON group in same time and there was statistical significance(<i>P</i><0.01). In LOM group at 8^th and 12^th wk, compared with DM group in the same period, the numbers of TUNEL positive RGCs decreased. The apoptosis index was significantly lower in LOM group compared with DM group in the same period(<i>P</i><0.01). Calcium ion concentration detection by laser confocal microscope: compared with CON group in same time points, at 8^th and 12^th week, DM group's calcium fluorescent staining intensity of RGCs markedly elevated and had significant differences.(<i>P</i><0.01). In LOM group, at 8^thand 12^th wk, calcium fluorescent staining intensity of RGCs markedly decreased and had statistical significance(<i>P</i><0.01).<p>CONCLUSION: The LOM played a protective role for RGCs in early stage of diabetic rats.