**Background:** Zebrafish (Danio rerio) are increasingly used as a model for ocular diseases due to their genetic and anatomical similarities to humans, rapid development, and transparent larvae that allow direct visualization of eye structures. This narrative review aims to provide an overview of zebrafish models for various ocular pathologies, including inherited retinal diseases, congenital malformations, acquired conditions, and infections, as well as the zebrafish's regenerative capacity.
**Methods:** The authors conducted a literature search on PubMed, focusing on articles published in the last 5 years (since 2018), with older references included for proof-of-concept or consolidated concepts. The review covers zebrafish ocular development, physiology, and models for anterior and posterior eye diseases, including cataracts, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and ocular infections.
**Key Results:** The review details numerous zebrafish models for ocular diseases:
- **Cataract:** Models include mutations in crystallin genes (crygc, cryga, crygb), aquaporins (aqp0a, aqp0b), dnase1l1l knockout, and rbm24 loss-of-function, all leading to lens opacity.
- **Glaucoma:** Models involve foxc1 knockdown (disrupted hyaloid vasculature), guca1c knockout (retinal ganglion cell apoptosis), cyp1b1 manipulation (altered ocular fissure closure), and H2O2-induced oxidative stress.
- **AMD:** Models include rp1l1 mutation (photoreceptor degeneration), ube3d knockdown (increased angiogenesis), fads2 deletion (enhanced apoptosis under light), and vhl mutants (neovascularization).
- **Diabetic retinopathy:** Hyperglycemia induced by glucose exposure (130 mM for 72 h) causes increased vessel diameter, VEGF mRNA levels, and ZO-1 disruption. Methylglyoxal exposure (1000 µM) also increases retinal vessel diameter and vascular density.
- **Retinitis pigmentosa:** Models include mutations in rhodopsin (RHO), pde6a, and rlbp1a, as well as light-induced retinal damage (13,000 lux for 24 h) causing photoreceptor degeneration.
- **Ocular infections:** Models include Zika virus (ZIKV) infection leading to microcephaly and retinal layer thickening, Mycobacterium marinum for ocular tuberculosis, and Staphylococcus aureus injection causing local infection with neutrophil and macrophage migration.
- **Regeneration:** Müller glia cells can de-differentiate and regenerate retinal neurons after injury, involving pathways such as TNFα, Ascl1a, Stat3, and Notch signaling.
**Clinical Implications:** Zebrafish models recapitulate key features of human ocular diseases, enabling study of genetic and environmental factors, drug screening, and regenerative mechanisms. However, limitations include differences in eye anatomy (e.g., thinner cornea, no corneal nerve fibers) and the inability to model certain conditions like dry eye or pterygium. The review emphasizes the potential for translational research, particularly in understanding disease mechanisms and testing novel therapies.