Conjunctival transforming growth factor-β2 and vascular endothelial growth factor in canine keratoconjunctivitis sicca: Baseline alterations, clinical associations, and response to 0.2% cyclosporine therapy

TL;DR

This study investigates how TGF-β2 and VEGF levels in dogs with dry eye disease change with cyclosporine treatment and their connection to disease severity and clinical outcomes.

Contribution

The study reveals how TGF-β2 and VEGF levels correlate with disease severity and treatment response in canine KCS.

Findings

CsA treatment improved tear production and clinical signs in dogs with KCS.

TGF-β2 levels increased with disease severity and correlated with chronic ocular changes.

VEGF levels decreased after CsA treatment, especially in severe cases.

Abstract

Transforming growth factor-β2 (TGF-β2) and vascular endothelial growth factor (VEGF) are key mediators of inflammation, fibrosis, and angiogenesis in ocular surface disease. However, their roles in canine keratoconjunctivitis sicca (KCS) are not well understood. This study aimed to compare conjunctival TGF-β2 and VEGF levels between healthy dogs and those with KCS, evaluate the effects of 6-week therapy with 0.2% cyclosporine A (CsA), and explore associations with clinical signs, Schirmer tear test-1 (STT-1), goblet cell density (GCD), and inflammatory cell infiltration.

Thirty-three dogs with KCS, classified as mild (n = 10), moderate (n = 10), or severe (n = 13), underwent ophthalmic exams, STT-1 measurements, and conjunctival biopsies before treatment (T0) and after 6 weeks of topical CsA therapy (T1). Fourteen healthy dogs served as controls. Conjunctival samples were analyzed for GCD, inflammatory cell counts, and TGF-β2 and VEGF levels using histology and enzyme-Linked Immunosorbent Assay. Clinical scoring and corneal vascular quantification were performed using standardized protocols. Statistical comparisons were made within and between groups, as well as through correlation analyses.

CsA significantly increased STT-1 in all KCS grades and improved selected clinical signs. GCD in KCS dogs increased at T1, reaching levels comparable to controls, although not statistically significant. Neutrophils were the only inflammatory cells to significantly decrease after treatment. Overall, TGF-β2 levels did not differ between controls and KCS dogs; however, concentrations increased with disease severity and showed a positive correlation with lymphocyte counts and corneal melanosis, and a negative correlation with GCD. VEGF levels were mildly elevated in KCS but decreased significantly following CsA treatment, especially in severe cases, and correlated positively with corneal melanosis and negatively with corneal vessel counts. A positive correlation was observed between TGF-β2 and VEGF.

Topical 0.2% CsA improves tear production, GCD restoration, and various clinical signs in canine KCS. TGF-β2 seems to have a pro-inflammatory and profibrotic role, increasing with disease severity and linked to chronic ocular surface changes. CsA effectively decreases VEGF, especially in severe KCS, indicating partial modulation of angiogenic pathways. Longer treatment durations may be necessary to influence TGF-β2-mediated tissue remodeling.

Figures