Changes in the Expression of SMARCA4 in a Rat Model of Ocular Hypertension

dc.creatorWorley, Josh
dc.creatorStankowska, Dorota
dc.creatorKodati, Bindu
dc.creatorKrishnamoorthy, Raghu
dc.description.abstractTitle: Changes in the Expression of SMARCA4 in a Rat Model of Ocular Hypertension Purpose: SMARC4 (BRG1) is an ATP-dependent chromatin remodeling protein belonging to the SWI/SNF family of proteins involved in regulation of gene expression in numerous cell types in the body. The purpose of this study was to determine changes in the expression of SMARCA4 in the retina following intraocular pressure (IOP) elevation by the Morrison model in Brown Norway rats. We hypothesize that SMARCA4 expression may modulate the expression of the key genes involved in the neurodegenerative changes seen secondary to IOP elevation. Methods: The Morrison model of ocular hypertension (by injection of hypertonic saline through the episcleral veins) was utilized to unilaterally elevate the IOP in Brown Norway rats. IOP was elevated in the left eye of three retired breeder Brown Norway rats, with the right eye serving as the corresponding contralateral control. Rats were maintained for 2 weeks following IOP elevation and IOP measurements were carried out twice per week. Rats were subsequently euthanized, and retinal sections were obtained from both IOP-elevated and contralateral control eyes. Immunohistochemical analysis of SMARCA4 expression was carried out by immunostaining. Following confocal microscopy imaging, the intensity of immunofluorescence was quantified with the ImageJ software (NIH), and compared between IOP elevated and control eyes. Results: Immunohistochemical analysis revealed an appreciable decrease in the expression of SMARCA4 in retinal sections in two out of three rats, mainly the nerve fiber layer (by 47 to 57%), ganglion cell layer (by 18 to 40%) and inner plexiform layer (by 9 to 19%) in IOP elevated rat eyes compared to control eyes. One out of three tested rats showed a modest increase in immunostaining for SMARCA4 in the nerve fiber layer, ganglion cell layer and inner plexiform layer. Ongoing experiments will replicate these findings in order to generate statistically significant data. Conclusion: Changes in SMARCA4 expression could serve to regulate the expression of gene contributing to neurodegenerative effects due to elevated IOP. Understanding the role of SMARCA4 may allow us to better understand and address the mechanisms involved in glaucomatous neurodegeneration.
dc.titleChanges in the Expression of SMARCA4 in a Rat Model of Ocular Hypertension