Reno-ocular syndromes: pathophysiological mechanisms linking kidney and ocular disorders

The frequent association between renal and ocular anomalies suggests a common pathophysiological axis between the genetic and molecular mechanisms of the kidneys and multiple ocular structures during tissue formation, differentiation, and remodeling. The search was conducted in the PubMed, SciELO, Scopus, and Web of Science databases. This review article focuses on the common molecular and genetic bases of renal and ocular involvement in both systemic diseases and rare syndromes. The interdependence between renal and ocular morphogenesis is mediated by conserved molecular mechanisms, notably the Bone Morphogenetic Protein-7 (BMP-7) pathway, which regulates nephrogenesis and lens development, and the transcription factor Paired Box 2 (PAX2), which is essential for the formation of the genitourinary tract and the optic nerve. Shared expression of molecular components and dependency on their expression for the integrity of both the eye and the kidney lie in the stability of extracellular matrix components, specifically through laminin β2 (LAMB2) and type IV collagen, whose pathogenic variants underlie syndromic phenotypes such as Pierson and Alport syndromes. In addition, ciliopathies, developmental disorders, immune-mediated diseases, and inborn errors of metabolism, including Fabry disease, cystinosis, and primary hyperoxaluria, promote parallel injury to renal and ocular tissues through mechanisms involving abnormal cellular signaling, metabolite accumulation, complement activation and systemic inflammation. These mutual pathways affect diverse ocular structures, including the cornea, lens, retina, optic nerve, and basement membranes. Furthermore, the presence of the kidney-retina axis enables the use of the retina as a sentinel organ, allowing for non-invasive evaluation of glomerular microvasculature by means of high-resolution imaging technologies of retinal vessels. The kidneys and eyes share several genetic, developmental, structural, metabolic, and immunological mechanisms that explain the frequent association of congenital anomalies and acquired lesions in these organs and the associated diagnostic and prognostic implications.