Biological sex is an important aspect of all medical research and can significantly impact study outcomes. Previous scientific studies have shown that female mice carrying a retinitis pigmentosa disease, like that found in humans, display more severe disease progression compared to males. A new research article by LRL scientists, published in Redox Biology, set out to explain the underlying reasons for this previously observed difference in disease severity between the sexes.

First, we confirmed that the difference in disease phenotype emerges at an age corresponding to adolescence in humans – more scientifically put, after mice have reached sexual maturity. In subsequent experiments, we mechanistically demonstrated that this sex difference is likely explained by differential retinal oxidative stress. More specifically, female retinitis pigmentosa mice exhibit stronger retinal lipid peroxidation.

Mass spectrometry–based tissue lipid profiling (lipidomics) revealed that the basal levels of long-chain polyunsaturated fatty acid–containing lipids, which are structurally vulnerable to oxidation, are higher in female mice than in males.

Based on our results, we can confidently conclude that lipid peroxidation contributes to the accelerated progression of retinitis pigmentosa in female mice compared to males. In contrast, the generally higher levels of long-chain polyunsaturated fatty acids in female retinas remain a correlative finding. Their direct significance to retinal disease progression was not further explored in the Redox Biology study and remains to be tested in future work.

As a take-home message, this study reinforces the importance of carefully considering and reporting the sex of laboratory animals. Given that recent work by Rowe et al., published in Science Advances (2025), has additionally demonstrated that female hormones can aggravate retinal degeneration, further investigations into this topic are warranted. Whether this phenomenon extends to other mammalian species, including humans, represents an important future direction for research.

Read more at: https://www.sciencedirect.com/science/article/pii/S2213231725005002?via%3Dihub#sec8

Blog by: Katri Vainionpää

(edited by HL)

Photo attribute: FreePik