Ciliary Neurotrophic Factor in Patients with Primary Open-angle Glaucoma and Age-related Cataract

Overview

Journal Mol Vis

Specialties Cell Biology
Molecular Biology
Ophthalmology

Date 2017 Dec 12

PMID 29225456

Citations 18

Authors

Alexander A Shpak

Alla B Guekht

Tatiana A Druzhkova

Ksenia I Kozlova

Natalia V Gulyaeva

Affiliations

Soon will be listed here.

Abstract

Purpose: To 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).

Methods: CNTF 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.

Results: The 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.

Conclusions: The 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.

Citing Articles

Advances in Neuroprotection in Glaucoma: Pharmacological Strategies and Emerging Technologies.

Wang L, Huang C, Lin I Pharmaceuticals (Basel). 2024; 17(10).

PMID: 39458902 PMC: 11510571. DOI: 10.3390/ph17101261.

Novel ancestry-specific primary open-angle glaucoma loci and shared biology with vascular mechanisms and cell proliferation.

Lo Faro V, Bhattacharya A, Zhou W, Zhou D, Wang Y, Lall K Cell Rep Med. 2024; 5(2):101430.

PMID: 38382466 PMC: 10897632. DOI: 10.1016/j.xcrm.2024.101430.

Interaction of S100A6 Protein with the Four-Helical Cytokines.

Kazakov A, Deryusheva E, Rastrygina V, Sokolov A, Permyakova M, Litus E Biomolecules. 2023; 13(9).

PMID: 37759746 PMC: 10526228. DOI: 10.3390/biom13091345.

Neuroprotection in Glaucoma: Basic Aspects and Clinical Relevance.

Kuo C, Liu C J Pers Med. 2022; 12(11).

PMID: 36579616 PMC: 9697907. DOI: 10.3390/jpm12111884.

Clinical Tear Fluid Proteomics-A Novel Tool in Glaucoma Research.

Nattinen J, Aapola U, Nukareddy P, Uusitalo H Int J Mol Sci. 2022; 23(15).

PMID: 35897711 PMC: 9331117. DOI: 10.3390/ijms23158136.

References

Kliuchnikova A, Samokhina N, Ilina I, Karpov D, Pyatnitskiy M, Kuznetsova K . Human aqueous humor proteome in cataract, glaucoma, and pseudoexfoliation syndrome. Proteomics. 2016; 16(13):1938-46. DOI: 10.1002/pmic.201500423. View

Yu S, Tanabe T, Yoshimura N . A rat model of glaucoma induced by episcleral vein ligation. Exp Eye Res. 2006; 83(4):758-70. DOI: 10.1016/j.exer.2006.03.014. View

Ilzecka J . Increased serum CNTF level in patients with amyotrophic lateral sclerosis. Eur Cytokine Netw. 2003; 14(3):192-4. View

Valter K, Bisti S, Gargini C, Di Loreto S, Maccarone R, Cervetto L . Time course of neurotrophic factor upregulation and retinal protection against light-induced damage after optic nerve section. Invest Ophthalmol Vis Sci. 2005; 46(5):1748-54. DOI: 10.1167/iovs.04-0657. View

Laaksovirta H, Soinila S, Hukkanen V, Roytta M, Soilu-Hanninen M . Serum level of CNTF is elevated in patients with amyotrophic lateral sclerosis and correlates with site of disease onset. Eur J Neurol. 2008; 15(4):355-9. DOI: 10.1111/j.1468-1331.2008.02080.x. View

Ohashi Y, Motokura M, Kinoshita Y, Mano T, Watanabe H, Kinoshita S . Presence of epidermal growth factor in human tears. Invest Ophthalmol Vis Sci. 1989; 30(8):1879-82. View

Noma H, Funatsu H, Mimura T, Harino S, Hori S . Aqueous humor levels of vasoactive molecules correlate with vitreous levels and macular edema in central retinal vein occlusion. Eur J Ophthalmol. 2009; 20(2):402-9. DOI: 10.1177/112067211002000222. View

Zhang W, Prausnitz M, Edwards A . Model of transient drug diffusion across cornea. J Control Release. 2004; 99(2):241-58. DOI: 10.1016/j.jconrel.2004.07.001. View

Sarup V, Patil K, Sharma S . Ciliary neurotrophic factor and its receptors are differentially expressed in the optic nerve transected adult rat retina. Brain Res. 2004; 1013(2):152-8. DOI: 10.1016/j.brainres.2004.03.030. View

10.

Pasquin S, Sharma M, Gauchat J . Ciliary neurotrophic factor (CNTF): New facets of an old molecule for treating neurodegenerative and metabolic syndrome pathologies. Cytokine Growth Factor Rev. 2015; 26(5):507-15. DOI: 10.1016/j.cytogfr.2015.07.007. View

11.

MacLaren R, Buch P, Smith A, Balaggan K, Macneil A, Taylor J . CNTF gene transfer protects ganglion cells in rat retinae undergoing focal injury and branch vessel occlusion. Exp Eye Res. 2006; 83(5):1118-27. DOI: 10.1016/j.exer.2006.05.019. View

12.

Kuiper J, Dam-van Loon N, Domanian A, Schellekens P, Nierkens S, Radstake T . Correlation between measurement of IL-10 and IL-6 in paired aqueous humour and vitreous fluid in primary vitreoretinal lymphoma. Acta Ophthalmol. 2015; 93(8):e680-1. DOI: 10.1111/aos.12733. View

13.

Skaper S . The neurotrophin family of neurotrophic factors: an overview. Methods Mol Biol. 2012; 846:1-12. DOI: 10.1007/978-1-61779-536-7_1. View

14.

Horwath-Winter J, Kirchengast S, Meinitzer A, Wachswender C, Faschinger C, Schmut O . Determination of uric acid concentrations in human tear fluid, aqueous humour and serum. Acta Ophthalmol. 2008; 87(2):188-92. DOI: 10.1111/j.1755-3768.2008.01215.x. View

15.

Liu X, Clark A, Wordinger R . Expression of ciliary neurotrophic factor (CNTF) and its tripartite receptor complex by cells of the human optic nerve head. Mol Vis. 2007; 13:758-63. PMC: 2768760. View

16.

Li R, Wen R, Banzon T, Maminishkis A, Miller S . CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium. PLoS One. 2011; 6(9):e23148. PMC: 3166283. DOI: 10.1371/journal.pone.0023148. View

17.

Dikovskaya M, Trunov A, Chernykh V, Korolenko T . Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development. Int J Circumpolar Health. 2013; 72. PMC: 3753133. DOI: 10.3402/ijch.v72i0.21087. View

18.

Ecker S, Hines J, Pfahler S, Glaser B . Aqueous cytokine and growth factor levels do not reliably reflect those levels found in the vitreous. Mol Vis. 2011; 17:2856-63. PMC: 3224830. View

19.

Lass J, Walter E, Burris T, Grossniklaus H, Roat M, Skelnik D . Expression of two molecular forms of the complement decay-accelerating factor in the eye and lacrimal gland. Invest Ophthalmol Vis Sci. 1990; 31(6):1136-48. View

20.

Zhang K, Hopkins J, Heier J, Birch D, Halperin L, Albini T . Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration. Proc Natl Acad Sci U S A. 2011; 108(15):6241-5. PMC: 3076847. DOI: 10.1073/pnas.1018987108. View