Research Article: Proteomic profiling of spontaneous myopia in 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.
Introduction:
Myopia has emerged as a growing global concern in recent decades, with East Asia being particularly affected. In China, the incidence of myopia among adolescents aged 6 to 17 is 37.4% ( 1 ), while among high school students aged 16 to 18, the incidence rises to 84.8% ( 2 ). Notably, the prevalence of high myopia in adolescents is as high as 19.3% ( 2 ). Although myopic symptoms can be corrected with spectacle lenses, the risks associated with high myopia are substantial, potentially leading to serious…
Read more