Neurotrophic factors in patients with primary open-angle glaucoma and age-related cataract. Part 1. Ciliary neurotrophic factor

Abstract

PurposeTo study the ciliary neurotrophic factor (CNTF) concentration in the aqueous humor (AH), lacrimal fluid (LF), and blood serum (BS) in patients with age-related cataract and primary open-angle glaucoma (POAG).MethodsCNTF concentrations were studied in 61 patients with age-related cataract, 55 patients with POAG combined with cataract, and 29 healthy controls (one eye in each person). Preliminary experiments permitted us to extend the minimum quantifiable value of the CNTF Quantikine enzyme-linked immunosorbent assay (ELISA) kit to 2.5 pg/ml.ResultsThe levels of CNTF in LF and BS did not differ in patients with cataract and controls. The CNTF concentration (pg/ml) in patients with POAG and cataract was lower than in patients with cataract (p<0.001) in AH (39.9±26.2 versus 57.2±25.6) and in LF (25.7±14.9 versus 39.9±18.0). The differences were not statistically significant for the CNTF level in BS (5.45±4.72 versus 5.96±4.92) and the AH/LF ratio (1.69±1.05 versus 1.58±0.70). In the patients with POAG, the AH level of CNTF correlated with the visual field index (Pearson’s correlation coefficient r = 0.35, p = 0.01). A statistically significant decrease in the AH and LF concentrations of CNTF was observed in patients in all stages of POAG compared with the cataract group. This decrease was particularly prominent in patients with severe glaucoma. Compared to patients with combined early and moderate stages of disease patients with advanced glaucoma showed an insignificant reduction in the median CNTF concentration in AH and LF. The serum CNTF concentration did not show any dependence on the glaucoma stage. The CNTF concentration in the AH strongly correlated with the CNTF concentration in the LF (r=0.71, p<0.000). A formula was suggested to calculate the concentration of CNTF in AH based on the CNTF concentration in LF.ConclusionsThe CNTF concentration is reduced in the AH and LF of patients with POAG, especially in those with severe visual field loss. The CNTF concentration in AH and LF showed a strong correlation, and this phenomenon opens up new options for a noninvasive estimation of the CNTF concentration in AH. The CNTF concentration established in the AH, LF, and BS of patients with age-related cataract can serve as normative data for persons older than 50 years old.

3D cell-laden polymers to release bioactive products in the eye

“…Long-term treatment with CNTF could beneficially impact the pathology of glaucoma. CNTF levels are reduced in the aqueous humor and lacrimal fluid of patients with primary open-angle glaucoma (Shpak et al, 2017). CNTF is also released by retinal glial cells in response to injury and it promotes retinal ganglion cell survival.…”

The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration

“…However, administration of exogenous CNTF significantly extends the activation time of STAT3 ( Ji et al, 2004 ). The CNTF concentration is decreased in the aqueous humor, lacrimal fluid and blood serum in patients with primary open–angle glaucoma (POAG); interestingly, the lowest levels of this neurotrophic factor positively correlate with a more advanced state of the disease ( Shpak et al, 2017 ; Table 1 ). Interestingly, the NT-501 ECT (encapsulated cell therapy) implant, a device containing a genetically modified CNTF-secreting cell line, is under evaluation in 60 POAG patients enrolled in an ongoing randomized, sham controlled, masked phase II clinical study (NCT02862938) ( Thanos et al, 2004 ; Barar et al, 2016 ; Table 2 and Figure 3 ).…”

Current Medical Therapy and Future Trends in the Management of Glaucoma Treatment

“…e CNTF concentration was reduced in aqueous humour and lacrimal fluid of patients with primary openangle glaucoma, especially in those with severe visual loss [114]. CNTF is a promising target and its neuroprotective effect was evaluated in phase I study (NCT01408472) in patients with POAG who received intraocular implant NT-501 CNTF (made by Neurotech) into one eye.…”