Proteomic profiling of spontaneous myopia in guinea pigs

TL;DR

This study identifies proteomic and ocular differences in guinea pigs with spontaneous myopia, suggesting they could serve as a model for human high myopia.

Contribution

The novel contribution is the discovery of proteomic profiles and ocular traits in spontaneously myopic guinea pigs resembling human high myopia.

Findings

Spontaneously myopic guinea pigs showed more negative refractive error, longer axial length, and thinner retinal layers.

Proteomic analysis revealed upregulated complement activation and ferroptosis pathways in myopic retinas.

Plasma proteomics showed elevated VEGF pathway protein expression in spontaneously myopic guinea pigs.

Abstract

There is a subset of guinea pigs born with spontaneous myopia that exhibit fundus characteristics similar to those of high myopia. This study aimed to further identify the traits, including proteomic profiling of the retina and plasma, in this strain of guinea pigs.

Spontaneously myopic guinea pigs (n = 11) and hyperopic controls (n = 12) were screened from 2-week-old pigmented guinea pigs. Refractive error (RE) was measured using infrared eccentric photorefraction. Swept-source optical coherence tomography (SS-OCT) was employed to assess ocular biometrics in anterior segment mode, while posterior layer thicknesses and fundus images were obtained in posterior segment mode. Retinal activity was assessed using ffERG. H&E staining and TUNEL assay were performed, with the latter assessing apoptosis in the retina and optic disc head. Retinal and plasma samples were further analyzed using rapid data-independent acquisition (Rapid-DIA) proteomics.

Compared to hyperopic eyes, spontaneously myopic eyes displayed a more negative RE (p < 0.0001), significantly elongated AL (p = 0.004), and increased VCD (p < 0.0001). Moreover, spontaneously myopic eyes exhibited significantly thinner retina (p = 0.008), choroid (p = 0.0006), and sclera (p = 0.002). All spontaneous myopia cases displayed a tessellated fundus, whereas no such fundus was observed in hyperopia. ERG responses were similar between the two groups. TUNEL staining revealed significantly increased apoptosis in the outer nuclear layer of myopic retinas. Proteomic analysis identified upregulated complement activation and ferroptosis-related pathways in myopic retinas, alongside reduced nitric oxide signaling protein expression. Plasma proteomics indicated elevated VEGF pathway protein expression in spontaneously myopic guinea pigs.

Spontaneously myopic guinea pigs showed high similarity to human high myopia in ocular parameters, fundus, and molecular pathways, suggesting the potential as an alternative model for high myopia research.

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