How Fish, Frogs and Squid Revealed the Secrets of the Eye Lens

The ocular lens is one of biology’s most elegant compromises: a living piece of biological glass that must remain perfectly transparent while staying metabolically active for a lifetime. A new review in Frontiers in Ophthalmology argues that aquatic species—fish, frogs, newts, squid, seals and even diving beetles—have quietly shaped nearly everything we know about this remarkable tissue over the past two centuries, from the physics of focusing light to the molecular choreography of organ loss during development.

The story begins with physics. Shortly after Thomas Young described visual optics and accommodation in the human eye in 1801, researchers turned to fish. In water, the cornea loses nearly all of its refractive power, so the lens must do the focusing alone. That simplification made the dense, spherical fish lens an ideal natural model. Ludwig Matthiessen exploited this in a landmark series of studies, showing that fish lenses lack spherical aberration and defining what became known as Matthiessen’s ratio: the focal length of the lens is roughly 2.55 times its radius. He even demonstrated that whales and dolphins, mammals that returned to the sea, convergently evolved the characteristic optics of fishes. Theodor Beer added a crucial twist: because fish lenses are so dense they cannot change shape, so they accommodate by moving within the eye instead.

Modern imaging has only deepened the appreciation of aquatic lens optics. Fish eyes typically have short focal lengths and large pupils to maximize light capture, which creates strong chromatic aberration—a serious problem for shallow-water species with vivid color vision. Their solution is a multifocal lens that focuses different wavelengths onto different planes, something the monofocal human lens does not do. Remarkably, the optics remain adjustable throughout life. In the cichlid fish Haplochromis burtoni, individuals raised under monochromatic light developed lenses with altered gradient refractive index properties, and in a related cichlid, the lens shifted toward monofocal optics in the dark-adapted state, presumably matching rod-dominated vision. How organelle-free fiber cells accomplish this optical tuning remains an open question.

Aquatic models have also become central to understanding myopia, the most common visual disorder in humans. When researchers covered the eyes of Nile tilapia with diffusers that induce form-deprivation myopia, the fish responded like birds and mammals, integrating visual input into the regulation of eye growth—without any change in lens optics. Zebrafish have since emerged as a genetic platform for emmetropization studies, with optical coherence tomography used to quantify eye dimensions and multiple myopia-related genes identified. The four-eyed fish Anableps, which sees simultaneously in air and water through a pear-shaped lens with distinct aerial and aquatic optical zones, and the sunburst diving beetle larva, whose tubular bifocal eyes scan the environment, illustrate the extraordinary range of solutions evolution has produced for the same focusing problem.

The lens’s transparency and high refractive power depend on crystallin proteins, and aquatic species provided the first evidence that these proteins were co-opted from metabolic enzymes and stress-response proteins—a foundational model for gene sharing. Fishes express all three ubiquitous vertebrate crystallin families, plus abundant methionine-rich γM-crystallins not found in terrestrial vertebrates. Comparative biochemistry revealed that α- and β-crystallins co-elute in fish lenses, suggesting interactions absent in mammals. Squid lenses, built from a single crystallin type descended from a glutathione S-transferase ancestor with 25 differentially expressed variants under positive selection, show that the same evolutionary strategy—recycling stress and detoxification genes—arose independently in invertebrates.

Temperature extremes have turned fish lenses into natural laboratories for protein stability. McFall-Ngai and Horwitz compared lenses from 12 species spanning physiological temperatures from -2°C in Antarctic icefish to 47°C in desert lizards, finding that species adapted to heat resisted temperature-induced opacity better, with α-crystallins most resistant to aggregation. The Antarctic toothfish, which lives at -2°C, has become a star model: its αA-crystallin carries a valine-to-threonine substitution that alters surface hydrophobicity and oligomer stability, and its γS-crystallin remains structurally stable up to 56-63°C—far above its physiological temperature. Its lens also stays clear after 48 hours at -12°C, while a tropical fish develops nuclear opacity at 0°C. Biophysical analysis of six toothfish γ-crystallins showed that the liquid-liquid phase separation underlying cold cataract depends on charged-residue interactions rather than thermal stability, offering a model for manipulating protein stability by design.

Zebrafish, with their duplicated teleost genomes, have dissected multifunctional proteins into separable roles. The single mammalian aquaporin 0 water channel exists as two zebrafish paralogs: Aqp0a serves as the primary water channel, while Aqp0b shows stronger auto-adhesion due to a single amino acid substitution. CRISPR mutants revealed that loss of Aqp0a prevents the developmental centralization of the lens nucleus, destabilizes the anterior suture, and produces age-related opacity—even though the maximum refractive index is still reached. Similarly, zebrafish carry two αB-crystallin paralogs with divergent expression: the lens-preferred αBa-crystallin doubles cataract incidence at 24 months when lost, suggesting it stabilizes other lens proteins during aging, while αA-crystallin acts as a stronger chaperone at zebrafish physiological temperatures. Far from being a complication, gene duplication provides a powerful tool for separating protein functions.

Aquatic species have illuminated lens development with unmatched precision. Zebrafish form their lens by delamination rather than invagination, never producing a hollow vesicle, yet cell fate mapping by Greiling and Clark showed that central placode cells become primary fiber cells while lateral cells become epithelium—a pattern conserved with the mouse. The most striking recent discovery came from CRISPR screening: the phospholipase gene plaat1 is required for fiber cell organelle removal in zebrafish, and knockout of the mouse ortholog Plaat3 produces the same organelle retention, revealing a conserved mechanism regulated by Hsf4 that targets organelle membranes for degradation. Because keratinocytes and erythrocytes also lose organelles during differentiation, understanding this process has significance far beyond the eye.

Regeneration is where aquatic species truly shine. Newts can regenerate a fully functional lens from dorsal iris pigment epithelial cells repeatedly, without diminishing capacity, and recent work shows macrophages facilitate the process. The African clawed frog regenerates its lens from corneal epithelial cells, even in post-metamorphic animals, and apoptosis is required for regeneration but not initial development. Perhaps most dramatic is the Mexican tetra, whose cave-dwelling populations evolved degenerate eyes over roughly 10,000 years: transplanting a surface-fish lens into a cave-fish embryo restored normal eye development, proving that lens signals sustain retinal growth. These systems are informing early efforts toward human lens regeneration.

Looking forward, the review points to zebrafish as a cost-effective aging model—roughly 27 percent of wildtype fish develop lens opacity by 18 months—and to expanding -omics approaches, including a single-cell transcriptomic atlas of the vertebrate lens and proteomics that quantifies over 13,000 proteins in the tiny zebrafish lens. Farmed fish, from salmon with diet-linked cataracts to lumpfish with prevalence approaching 100 percent, offer practical models for cataract prevention. Two hundred years after Matthiessen first measured a fish lens, aquatic species remain not just historical footnotes but active engines of discovery in lens biology, with direct implications for treating human blindness, myopia, and age-related cataract.

Subject of Research: Contributions of aquatic organisms to understanding the vertebrate ocular lens

Article Title: Contributions of aquatic organisms to understanding the vertebrate ocular lens

Article References: Posner, M. (2026). Contributions of aquatic organisms to understanding the vertebrate ocular lens. Frontiers in Ophthalmology, 6, Article 1900415. https://doi.org/10.3389/fopht.2026.1900415

Image Credits: AI Generated

DOI: 10.3389/fopht.2026.1900415

Keywords: ocular lens, aquatic models, zebrafish, crystallins, lens regeneration, myopia, cataract, Antarctic toothfish, lens development, comparative biology, Contributions, aquatic