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

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.

Spatiotemporal alterations of presynaptic elements in the retina after high intraocular pressure

A rat model of acute high intraocular pressure was established by injecting saline into the anterior chamber of the left eye. Synaptophysin expression was increased in the inner plexiform layer at 2 hours following injury, and was widely distributed in the outer plexiform layer at 3-7 days, and then decreased to the normal level at 14 days. This suggests that expression of this presynaptic functional protein experienced spatiotemporal alterations after elevation of intraocular pressure. There was no significant change in the fluorescence intensity and distribution pattern for synapse-associated protein 102 following elevated intraocular pressure. Synapse-associated protein 102 immunoreactivity was confined to the outer plexiform layer, while synaptophysin immunoreactivity spread into the outer plexiform layer and the outer nuclear layer at 3 and 7 days following injury. These alterations in presynaptic elements were not accompanied by changes in postsynaptic components.

Spectral domain optical coherence tomography crosssectional image of optic nerve head during intraocular pressure elevation

AIM: To analyze changes of the optic nerve head(ONH) and peripapillary region during intraocular pressure(IOP) elevation in patients using spectral domain optical coherence tomography(SD-OCT).METHODS: Both an optic disc 200×200 cube scan and a high-definition 5-line raster scan were obtained from open angle glaucoma patients presented with monocular elevation of IOP(≥30 mm Hg) using SD-OCT. Additional baseline characteristics included age, gender, diagnosis,best-corrected visual acuity, refractive error, findings of slit lamp biomicroscopy, findings of dilated stereoscopic examination of the ONH and fundus, IOP, pachymetry findings, and the results of visual field.RESULTS: The 24 patients were selected and divided into two groups: group 1 patients had no history of IOP elevation or glaucoma(n =14), and group 2 patients did have history of IOP elevation or glaucoma(n =10). In each patient, the study eye with elevated IOP was classified into group H(high), and the fellow eye was classified into group L(low). The mean deviation(MD)differed significantly between groups H and L when all eyes were considered(P =0.047) and in group 2(P =0.042), not in group 1(P =0.893). Retinal nerve fiber layer(RNFL) average thickness(P =0.050), rim area(P =0.015),vertical cup/disc ratio(P =0.011), cup volume(P =0.028),inferior quadrant RNFL thickness(P =0.017), and clockhour(1, 5, and 6) RNFL thicknesses(P =0.050, 0.012, and0.018, respectively), cup depth(P =0.008), central prelaminar layer thickness(P =0.023), mid-inferior prelaminar layer thickness(P =0.023), and nasal retinal slope(P =0.034)were significantly different between the eyes with groups H and L.CONCLUSION:RNFLaveragethickness,rim area,vertical cup/disc ratio, cup volume, inferior quadrant RNFL thickness, and clock-hour(1, 5, and 6) RNFL thicknesses significantly changed during acute IOP elevation.

Enzymatic Histochemistry of Retina with Experimental Intraocular Pressure Elevation in Rabbits

To investigate the pathogenesis of retina lesions caused by intraocular pressure elevation, activities and distribution of enzymes in retina including lactic dehydrogenase (LDH), succinate dehydrogenase (SDH), adenosinetriphosphatase (ATPase), acid phosphatase (ACP), cholinesterase (ChE), cytochrome oxidase(CCO),nucleotidase (5'-Nase) and glucose-6-phosphatase (G6Pase) were determined histochemically in 30 rabbits. It was found that 1) in the early stage of intraocular pressure elevation, the activities of LDH, SDH, ATPase, ACP, and ChE in retina were increased, while the activities of CCO,5'-Nase decreased;2)in thelate stage of intraocular pressure elevation, the activities of all these enzymes but ACP, which showed a reduced activity, were close to the normal level; 3) in superoxide dismutase.(SOD-CCE) treated group, except the slight increase of LDH and G6Pase activities,the activities of the remaining enzymes were near to normal. Our results suggest that the various histochemical changes in retina induced by intraocular pressure elevation were cornpensatory in the early stage and were beneficial to the supply of energy needed in retinal tissue andcellular metabolism;while in the late stage, the lesion of retina cells developed due to decompensation.SOD-CCE could alleviate the retinal lesions caused by intraocular pressure elevation, and can be used as auxiliary drug for the treatment of intraocular pressure elevation.