Abstract
PurposeThis is a retrospective study of primary open-angle glaucoma patients treated with the immunosuppressor FK506 (tacrolimus) after an organ transplant. We assessed whether FK506 might be a potential neuroprotector adjuvant in glaucoma therapy.Patients and methodsOrgan transplant patients treated with FK506 for one or more years between 2006 and 2017 at the University of Texas Medical Branch (UTMB) were enrolled. Those selected were patients older than or equal to 50 years of age and had an ophthalmological eye examination with or without diagnostic tests for primary open-angle glaucoma (POAG). Sixty-one eligible subjects were included in the study and matched with the non-FK506 control group for age, gender, race, and follow-up visits.ResultsA lower incidence of POAG was noted in the FK506-treated patients (15%) when compared to the non-FK506 group (22%), though not significant (p=0.34). Among POAG subjects, the average retinal nerve fiber layer (RNFL) thickness decreased at a rate of 1.4 µm per year (p=0.0001) in the non-FK506 control patients versus 0.4 µm per year (p=0.34) in the FK506 patients. The superior and inferior RNFL quadrants in the control non-FK506 group had a thinning of 2.2 µm and 2.3 µm per year, respectively, (p=0.003 and p=0.0001), while in the FK506 patients, there was no significant loss. In addition, RNFL thinning in nasal and temporal quadrant also showed less reduction in FK506-treated subjects but was not statistically significant (p=0.68 and p=0.93).ConclusionFK506 therapy offers a new promising avenue for neuroprotection in POAG patients and needs to be investigated further for use in conjunction with conventional glaucoma treatments.
Highlights
Glaucoma is considered to be one of the leading neurodegenerative disorders characterized by the loss of retinal nerve fiber layer (RNFL) at the optic nerve head due to the death of retinal ganglion cells (RGC) [1]
Among primary open-angle glaucoma (POAG) subjects, the average retinal nerve fiber layer (RNFL) thickness decreased at a rate of 1.4 μm per year (p=0.0001) in the non-FK506 control patients versus 0.4 μm per year (p=0.34) in the FK506 patients
In patients affected by primary open-angle glaucoma, the presence of inter-nucleosomal DNA fragmentation in the RGCs was found to be elevated 15.2 times compared to healthy eyes [3]
Summary
Glaucoma is considered to be one of the leading neurodegenerative disorders characterized by the loss of retinal nerve fiber layer (RNFL) at the optic nerve head due to the death of retinal ganglion cells (RGC) [1]. The mechanism underlying RGC death is still not fully understood, evidence suggest that RGCs die as a result of an apoptotic process with consequent chromatin condensation, DNA fragmentation, oxidative damage, and autophagic degeneration [2]. Observations concluded from experimental rodent models of glaucoma with elevated intraocular pressure (IOP) suggest RGC death is an apoptotic type of cell death [4,5,6]. RGC apoptosis is hypothesized to be initiated by several underlying mechanisms, such as an imbalance in calcium homeostasis, neurotrophin deprivation, glial activation, excitotoxicity, ischemia, or oxidative stress [5]. Active CaN causes dephosphorylation of the pro-apoptotic B-cell lymphoma 2 (Bcl2)-associated agonist of cell death (BAD) family member, which triggers cytochrome C release from the mitochondria to the cytosol, activating the caspase family of proteases thereby inducing apoptosis [11,12]
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