Hypoxia and Growth Factor Profiling in High Myopia: Linking HIF-1α Suppression and PDGF-BB Activation to Structural Degeneration

Salvador Mérida Mérida¹Enrique García Gen¹Carmen Desco^1,2,3Amparo Navea³Francisco Bosch Morell^1*

• ¹Universidad CEU Cardenal Herrera, Valencia, Spain
• ²Fundacion de Oftalmologia Medica de la Comunitat Valenciana, Valencia, Spain
• ³Instituto de la Retina y Enfermedades Oculares, Valencia, Spain

Introduction: High myopia is associated with structural and molecular changes in the eye, particularly involving hypoxia-responsive and fibrotic mediators. Growing evidence points to a subset of growth factors as central mediators of these alterations. Among these, our findings identify HIF-1α and PDGF-BB as key contributors to the progression of myopia. Methods: This cross-sectional study included 88 Caucasian patients undergoing cataract surgery, categorized into control, low myopia, and high myopia groups based on axial length. Clinical assessments involved interferometric axial length measurement, swept-source OCT for choroidal thickness, and maculopathy classification following IMI guidelines. Aqueous humor samples were collected intraoperatively and analyzed using multiplex Quantibody arrays to quantify HIF-1α, VEGF, HGF, PDGF-BB, IL-6, and IL-17. Statistical analyses included Kruskal–Wallis tests with Bonferroni correction and correlation analyses to explore associations between molecular profiles and clinical severity. Results: Patients with high myopia exhibited significantly reduced choroidal thickness and increased axial length (p < 0.01), along with a higher prevalence of degenerative maculopathy (71.9%). Molecular profiling revealed lower levels of HIF-1α and VEGF (p < 0.01), and elevated levels of PDGF-BB (p < 0.05), HGF, and IL-6 (p < 0.01) in the high myopia group. HIF-1α levels showed inverse correlations with disease severity, while PDGF-BB correlated positively with fibrotic markers. No significant differences were observed in IL-17 levels. Discussion: For the first time, this study identifies significant alterations in HIF-1α and PDGF-BB levels in high myopia, with consistent correlations to key clinical parameters such as axial length, choroidal thickness, and maculopathy severity. These findings indicate an association suggesting a shift from adaptive hypoxia signaling toward fibrotic remodeling in high myopia. The suppression of HIF-1α and upregulation of PDGF-BB suggest a molecular imbalance that may be associated with This is a provisional file, not the final typeset article structural degeneration. The integration of clinical imaging and aqueous humor profiling supports the potential of HIF-1α and PDGF-BB as biomarkers and therapeutic targets in pathological myopia.