To try to better understand this complex relationship among IOP, RGCs, and glaucoma, a variety of animal models designed to study the impact of IOP on the retina have been developed 17, 18, 19, 20. While reducing IOP can slow or arrest the progression of RGC loss, elevation of IOP alone does not determine if patients will develop glaucoma, and many patients with statistically elevated IOP do not develop glaucoma at all 16. Both human and animal studies suggest that it is very likely that both RGC function and retinal processing become abnormal prior to RGC death 6, 7, 8, 9, 10, 11, 12, 13, 14, but the specific pathophysiological mechanisms that initially injure RGCs are poorly understood.Įlevated intraocular pressure (IOP) is the most important risk factor associated with glaucoma and correlates with the onset and progression of disease 4, 5, 15. In glaucoma, the progression from visual dysfunction to overt vision loss is chronic and subtle, which creates multiple challenges in diagnosis, and in many cases profound and permanent vision loss has already occurred at the time of diagnosis 4, 5. This number includes over 3 million people in the United States, most of whom have primary open angle glaucoma (POAG) 2, 3.
Worldwide, glaucoma is a major cause of irreversible blindness, affecting over 70 million people 2. Glaucoma is a heterogenous group of optic neuropathies hallmarked by cupping of the optic nerve head and progressive death of retinal ganglion cells (RGCs), which results in a decrease and subsequent loss of vision 1. It is possible that this improved understanding of changes in RGC gene expression can ultimately lead to novel diagnostics and therapeutics for glaucoma. Furthermore, it is possible that IOP-based set points exist within RGCs to impact the direction of transcriptional change. These results suggest that the magnitude of IOP elevation has a critical impact on RGC transcriptional changes. Differentially expressed genes were markedly different between the 2 groups, and pathway analysis revealed frequently opposed responses between the IOP levels. RNA sequencing was used to compare the transcriptional environment at each IOP level. IOP was elevated to 2 distinct levels which were defined as Mild (IOP increase >1 mmHg and <4 mmHg) and Moderate (IOP increase ≥4 mmHg). We developed a 4-step immunopanning protocol to extract adult mouse RGCs with high fidelity and used it to isolate RGCs from wild type mice exposed to 2 weeks of IOP elevation generated by the microbead model. Despite the central importance of IOP, details of the impact of IOP elevation on RGC gene expression remain elusive.
Elevated intraocular pressure (IOP) is the major risk factor for glaucoma, a sight threatening disease of retinal ganglion cells (RGCs) and their axons.
0 kommentar(er)
