Effects and underlying mechanisms of repeated low-level red light on refractive development in Guinea pigs with...

To investigate the regulatory effects of repeated low-level red light (RLRL) on refractive development in guinea pigs with different refractive states and to explore the underlying mechanisms.

Two-week-old tricolored short-haired guinea pigs were used. Myopia progression was induced by continuously wearing a -10.00 D negative lens on the right eye, whereas hyperopia progression was induced by wearing a +5.00 D positive lens. For the myopia recovery model, the negative lens was removed after myopia induction. After successful modeling, animals were randomly assigned to corresponding RLRL intervention groups or control groups. The RLRL groups received daily irradiation with red light at a central wavelength of 644.9 nm, three times a day, 2 min per session. Refraction, axial length, choroidal thickness, OCTA-derived choroidal flow signal, and corneal curvature radius were measured at 0, 1, 2, and 4 weeks after intervention. In addition, choroidal tissues from guinea pigs in the myopia progression and hyperopia progression models were collected 2 days after RLRL intervention for transcriptome sequencing, and RT-qPCR was performed to validate selected differentially expressed genes. For phenotypic analyses, five guinea pigs per subgroup were included in the final analysis. For transcriptomic analysis, six guinea pigs per group were used.

In the myopia progression model, RLRL attenuated the myopic refractive shift (group-by-time interaction, P < 0.001) and was associated with greater choroidal thickness and higher OCTA-derived choroidal flow signal at selected time points, while axial length was transiently shorter only at week 2 (P = 0.041). In the hyperopia progression model, RLRL promoted the shift toward emmetropia (group-by-time interaction, P = 0.006), with lower hyperopic refraction at weeks 2 and 4 (both P < 0.05). Although axial length was greater at individual time points, the group-by-time interaction was not significant (P = 0.092); RLRL was also associated with a thinner choroid at week 4 (P = 0.013) and lower OCTA-derived choroidal flow signal at selected time points. In the myopia recovery model, RLRL accelerated refractive recovery (group-by-time interaction, P = 0.010), with a transiently shorter axial length at week 2 (P < 0.001) and higher OCTA-derived choroidal flow signal at weeks 2 and 4 (P = 0.003 and P = 0.019). Transcriptomic analysis identified 113 and 733 differentially expressed genes in the myopia and hyperopia progression RLRL models, respectively. Exploratory pathway analysis suggested possible inflammation-related choroidal response under myopic conditions and melanin metabolism- and extracellular matrix remodeling-related changes under hyperopic conditions. RT-qPCR confirmed downregulation of RGS1 in the myopia progression model (P = 0.007) and upregulation of TYRP1 and DCT in the hyperopia progression model (P = 0.007 and P = 0.033, respectively).

RLRL exerted refractive state-dependent effects on ocular growth in guinea pigs, attenuating myopic progression under myopic conditions and promoting refractive emmetropization under hyperopic conditions. Transcriptomic analyses further suggested that these effects may be associated with refractive state-dependent changes in the choroidal microenvironment, with inflammation-related responses mainly observed under myopic conditions and melanin metabolism-related changes mainly observed under hyperopic conditions.