Abstract
Purpose :
We have previously shown that peripheral blood mononuclear cells (PBMC) from glaucoma patients can degrade retinal ganglion cells (RGC) in immune deficient mice. Here we correlate the RGC loss in mice with ophthalmic metrics of donating patient.
Methods :
Blood samples were obtained from primary open angle glaucoma (POAG) patients without regard to disease state or rate of vision loss (n=20). In addition, samples were obtained from non-glaucomatous controls (n=10). Exclusion criteria were other retinal diseases (except AMD) autoimmune disease or neurodegenerative diseases. PBMC were isolated from these samples and transferred into immune deficient NOD/scid gamma (NSG) mice by intraperitoneal injection. Each mouse received PBMC from one donor only, creating an immunologic ‘avatar’ of the patient. After transfer mouse eyes received a microbead injection calibrated to cause mild, transient elevation of intraocular pressure (IOP). 50 days after PBMC transfer, RGC density was determined in retinal flat mounts using cresyl violet staining. Data were compared to clinical findings observed in the patients.
Results :
Transfer of human PBMC did not cause significant side effects. However, retinas of mice having received PBMC from POAG donors displayed significantly fewer RGC than those having received PBMC from controls (255±64.8 RGC/field vs. 341±131 RGC/field, p=0.027) in central area. Among donors with POAG, PBMC of those with more advanced disease caused less damage to the recipients’ RGC than PBMC with less advanced disease. Avatars of donors with a ganglion cell layer (GCL) thickness above the median displayed 197±60.9 RGC/field whereas those with GCL thickness below the median contained 282 ±75 RGC/field (p:0.017). Likewise, avatar mice of donors with visual field loss above the median displayed 296±62 RGC/field, significantly more than those having received PBMC from donors with more advanced field loss (204±84 RGC/field, p=0.045). Other clinical parameters, including maximum or average IOP of the patient, do not appear to be correlated with RGC loss in recipient mice.
Conclusions :
Conclusions: These findings confirm that transfer of PBMC obtained from glaucoma patients causes more damage to RGC in NSG mice than those of controls. Our data also indicate that immune reactions may be more pronounced in POAG patents with moderate disease than in those with advanced disease.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.