Evaluations of aqueous humor protein markers in different types of glaucoma

Abstract

To compare the concentrations of protein markers in aqueous humor (AH) of patients with primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), acute primary angle closure (APAC), and cataract without glaucoma as the control group. AH samples were collected at the beginning of surgery from 82 eyes of 82 patients who were divided into POAG (n = 23), CACG (n = 21), APAC (n = 19), and cataract groups (n = 19). The expression levels of interferon-gamma (IFN-γ), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17A (IL-17A), lymphotoxin-alpha (LT-α), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), brain derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-AA (PDGF-AA), vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-α) in AH were detected using a microsphere-based immunoassay. The AH levels of TNF-α, MMP-2, MCP-1, IFN-γ, and TIMP-1 in the APAC and CACG groups were significantly higher than those in control eyes. Additionally, the AH levels of interleukin-6 (IL-6) and VEGF in the APAC group were significantly higher than those in the control group (CG). The interleukin-8 (IL-8) levels in patients with POAG were significantly higher than those in control eyes, whereas the LT-α levels were significantly lower than those in control eyes. IL-6 levels were significantly correlated with the coefficient of variation (CV), whereas IL-6 levels were significantly negatively correlated with the frequency of hexagonal cells (HEX) and corneal endothelial cell density (CD). The levels of TNF-α, MMP-2, MCP-1, IFN-γ, TIMP-1, IL-6, IL-8, VEGF, and LT-α were different among the three types of glaucoma. These different types of glaucoma may be caused by various pathogeneses, which opens avenues for further investigation into the pathogenesis of glaucoma and discoveries new targets and pathways for the treatment of glaucoma.

Relative ability of aqueous humor from dogs with and without primary angle‐closure glaucoma and ADAMTS10 open‐angle glaucoma to catalyze or inhibit collagenolysis

“…Therefore, it is unclear whether this study's findings represent part of the pathogenesis of disease or the consequences of chronic IOP elevation, vascular dysregulation, inflammation, or other changes accompanying CPACG 1 . Interestingly, however, recent work in people has demonstrated that AH from individuals with both acute and chronic angle closure contains similar levels of MMPs and TIMPs (and that these levels are elevated in comparison with normal eyes or eyes with POAG) 70 . Regardless of their cause, findings of the current study may provide justification for sampling of dogs in earlier stages of disease and may also contribute to the development of new therapies for dogs with CPACG in later stages of disease.…”

“…1 Interestingly, however, recent work in people has demonstrated that AH from individuals with both acute and chronic angle closure contains similar levels of MMPs and TIMPs (and that these levels are elevated in comparison with normal eyes or eyes with POAG). 70 Regardless of their cause, findings of the current study may provide justification for sampling of dogs in earlier stages of disease and may also contribute to the development of new therapies for dogs with CPACG in later stages of disease. For example, elucidating changes in AH in later stages of disease could lead to improved outcomes for glaucoma filtration surgeries in later-stage patients, since failure of filtering blebs may be linked to constant exposure to profibrotic mediators like TIMPs in glaucomatous AH.…”

“…However, it is also possible that differences in pathogenesis between CPACG and ADAMTS10-OAG are the cause of the disparity in results, particularly since changes in AH MMPs and TIMPs do not seem to be consistent across different types of glaucoma in people. 39,70 If eyes with ADAMTS10-OAG do not undergo the same MMP-and TIMP-modulated ECM modification as eyes with CPACG or glaucomatous human eyes, this could partially explain the lack of effect of netarsudil on IOP in dogs with ADAMTS10-OAG. 74 Netarsudil, a Rho kinase inhibitor, is a potent antihypertensive drug in human eyes and is thought to work via multiple mechanisms, one of which involves blunting transforming growth factor beta-induced changes in TM ECM mediated by MMPs and TIMPs.…”

“…Breed‐specific factors may also have influenced results, since all ADAMTS‐ OAG dogs were Beagles as were their wild‐type and homozygote comparators. However, it is also possible that differences in pathogenesis between CPACG and ADAMTS10 ‐OAG are the cause of the disparity in results, particularly since changes in AH MMPs and TIMPs do not seem to be consistent across different types of glaucoma in people 39,70 . If eyes with ADAMTS10 ‐OAG do not undergo the same MMP‐ and TIMP‐modulated ECM modification as eyes with CPACG or glaucomatous human eyes, this could partially explain the lack of effect of netarsudil on IOP in dogs with ADAMTS10 ‐OAG 74 .…”

Expression of IL-4 and IL-12 in the aqueous humor of patients with chronic primary angle-closure glaucoma

“…Subsequently, several studies reported abnormalities in serum cytokines, antibodies, and complement systems, and found that cytokine-mediated immune and inflammatory responses play an important role in the process of glaucomatous optic neuropathy. Notably, the aqueous humor of patients with glaucoma has higher concentrations of cytokines, such as IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor, and interferon-α, compared to healthy individuals ( 11 , 12 ). Yin ( 13 ) found that the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor -β2 were significantly higher in the aqueous humor of patients with POAG than in those of patients with cataract.…”