Glaucoma through Animal’s Eyes: Insights from the Evolution of Intraocular Pressure in Mammals and Birds

SIMPLE SUMMARY: Understanding how a disease evolved across the animal kingdom could help us better understand the disease and might lead to novel methods for treatment. Here, we studied the evolution of glaucoma, an irreversible eye disease, in mammals and birds, by studying the evolution of intraocular pressure (IOP), a central driver of glaucoma, and searching for associations between life history traits and IOP. Our results revealed that IOP is a taxa-specific trait that is higher in some species than in others. Higher IOPs appear to have evolved multiple times in mammals and birds. Higher IOPs were found in mammals with higher body mass and in aquatic birds. We also found that higher IOPs evolved through stabilizing selection, with the optimum IOP in mammals and birds being 17.67 and 14.31 mmHg, respectively. This supports the hypothesis that higher IOPs may be an adaptive trait for certain animals. Focusing on species with higher IOPs but no evidence of glaucoma may help identify glaucoma-resistant adaptations, which could be developed into human therapies. ABSTRACT: Glaucoma, an eye disorder caused by elevated intraocular pressure (IOP), is the leading cause of irreversible blindness in humans. Understanding how IOP levels have evolved across animal species could shed light on the nature of human vulnerability to glaucoma. Here, we studied the evolution of IOP in mammals and birds and explored its life history correlates. We conducted a systematic review, to create a dataset of species-specific IOP levels and reconstructed the ancestral states of IOP using three models of evolution (Brownian, Early burst, and Ornstein–Uhlenbeck (OU)) to understand the evolution of glaucoma. Furthermore, we tested the association between life history traits (e.g., body mass, blood pressure, diet, longevity, and habitat) and IOP using phylogenetic generalized least squares (PGLS). IOP in mammals and birds evolved under the OU model, suggesting stabilizing selection toward an optimal value. Larger mammals had higher IOPs and aquatic birds had higher IOPs; no other measured life history traits, the type of tonometer used, or whether the animal was sedated when measuring IOP explained the significant variation in IOP in this dataset. Elevated IOP, which could result from physiological and anatomical processes, evolved multiple times in mammals and birds. However, we do not understand how species with high IOP avoid glaucoma. While we found very few associations between life history traits and IOP, we suggest that more detailed studies may help identify mechanisms by which IOP is decoupled from glaucoma. Importantly, species with higher IOPs (cetaceans, pinnipeds, and rhinoceros) could be good model systems for studying glaucoma-resistant adaptations.