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

Vet World Vol.19 January-2026 Article - 21

Research Article

Veterinary World, 19(1): 295-309

https://doi.org/10.14202/vetworld.2026.295-309

Bianca Eidt Rodrigues¹, Alexandre Pinto Ribeiro¹, Tiago Barbalho Lima², Alcyjara Rego Costa², Marvin Paulo Lins³, and Luis Jhordy Alfaro Quillas¹

1. Faculdade de Medicina Veterinária, Universidade Federal de Mato Grosso, Mato Grosso, Cuiabá, Brazil.

2. Departamento de Clínica Veterinária, Hospital Veterinário Universitário, Universidade Estadual do Maranhão, São Luíz, Maranhão, Brazil.

3. Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso, Cuiabá, Brazil.

Background and Aim: 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.

Materials and Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: canine keratoconjunctivitis sicca, cyclosporine therapy, goblet cell density, ocular surface inflammation, tear film biomarkers, transforming growth factor-β2, vascular endothelial growth factor, veterinary ophthalmology.

How to cite this article: Rodrigues BE, Ribeiro AP, Lima TB, Costa AR, Lins MP, Quillas LJA. 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. Vet World. 2026;19(1):295–309.

Received: 27-08-2025 Accepted: 04-12-2025 Published online: 25-01-2026

Corresponding author: Alexandre Pinto Ribeiro E-mail: alexandre.aleribs@gmail.com

DOI: 10.14202/vetworld.2026.295-309

Copyright: Rodrigues, et al. This article is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.