Abstract
Purpose :
Glaucomatous optic neuropathy results in progressive irreversible vision loss. The role of immune imbalance in mediating optic nerve degeneration is less understood. We investigated the types of infiltrating immune cells and soluble factors in aqueous humour (AH) and their relationship with disease severity in patients with primary glaucoma (GL).
Methods :
AH was collected from GL and cataract (control) patients during surgical intervention without deviating from standard of care, following written, informed consent and prior approval by the institutional ethics committee. GL patients were grouped based on disease severity (Visual Field Index score and vertical cup to disc ratio - vCDR). Cells from AH (ctrl n=9, GL n=15) were phenotyped using fluorochrome conjugated antibodies specific for leukocytes (CD45), T cells (CD3), B cells (CD19), neutrophils (CD66b), monocytes (CD14), Natural Killer cells (NK; CD56) and NKT cells (CD3+ CD56+) by flow cytometry. Soluble factors in AH (ctrl n=20, GL n=55; non-severe n=25, severe n=30) were measured by multiplex ELISA.
Results :
Significantly (*P<0.05) higher proportions of *CD19+, *CD56+ and CD3+ cells were observed in AH of patients with severe forms of GL compared to non-severe forms and controls. CD19+ cells were inversely related to VFI score (*r = -0.668) and positively related with vCDR (*r = 0.655). Similarly, CD56+ cells correlated negatively with VFI score (*r = -0.679) and positively with vCDR (*r = 0.756). CD19+ cell numbers showed association with AH sFasL (*r = -0.523) and Eotaxin (*r = 0.563) levels. CD56+ cell numbers showed association with AH sICAM1 (*r = 0.587) and sFasL (*r = -0.598) levels. *sFasL, *IP-10 and *bFGF were lower in AH of severe patients compared to non-severe. Factors associated with neurodegeneration such as *NGAL, *Eotaxin, *MMP2, *IL-8, *sICAM1, *Perforins and *Granzymes were high in GL AH.
Conclusions :
Increased B and NK cells infiltration, along with decreased neuroprotective factors in AH are associated with severe forms of GL may suggest their pathogenic role in optic nerve degeneration. The observed increase in soluble immune factors with ability to facilitate neurodegeneration may have a causal relationship with disease severity. Hence, targeted immunomodulation might be beneficial in the management of glaucoma.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.