Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia

Biomolecules · 5 authors, 4 centres

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TL;DR

This preclinical study used monocular −10 D rigid gas-permeable contact lenses in 2-week-old guinea pigs (n = 8) to induce myopia and then tracked recovery after lens removal, showing bidirectional regulation of RPE Bmp2 gene expression.

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Two-week-old pigmented guinea pigs wore monocular −10 D rigid gas-permeable contact lenses for one week to induce myopia, followed by a recovery period after lens removal. Interocular differences in axial length and refractive error became significant after 3 and 7 days of lens wear, with choroidal thinning significant at day 7. After lens removal, axial length and refractive error normalized within 7 days, while choroidal thickening remained significant at day 7 before normalizing by day 14. Scleral thickness showed no significant interocular changes. RPE Bmp2 and Id3 expression were significantly downregulated after 1 day and 7 days of lens wear, and Bmp2 increased while Nog decreased 1 day after lens removal, with no Id3 change during recovery. The authors conclude that the CL model is a valid alternative to spectacle lens models for inducing myopia in young guinea pigs and that the bidirectional Bmp2 changes implicate BMP2 signaling in defocus-driven eye growth regulation consistent with prior chick studies.

STUDY TYPE

other

SPECIALTY

ophthalmology

SUMMARISED BY

AI pipeline

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ORIGINAL PAPER

PMC10526436

Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia

Biomolecules

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ABSTRACT

Purpose: We previously reported differential gene expression of the bone morphogenetic protein 2 ( Bmp2 ) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia. Methods: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular −10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2 , Id3 , and Nog genes. Results: Mean interocular differences (treated—control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia ( p < 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear ( p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day ( p = 0.012 and 0.016) and 7 days ( p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day ( p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation.

CITATION EXPORT

So Goto, Yan Zhang, Sonal Aswin Vyas et al.. Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia. Biomolecules. (2023). https://doi.org/10.3390/biom13091373

AUTHORS

5 · 4 CENTRES

So Goto, Yan Zhang, Sonal Aswin Vyas, Qiurong Zhu, Christine F. Wildsoet

1Herbert Wertheim School Optometry and Vision Science, University of California, Berkeley, CA 94720, USA
2Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita 565-0871, Japan
3Department of Ophthalmology, National Hospital Organization, Tokyo Medical Center, Meguro-ku, Tokyo 152-8902, Japan
4Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA

EDITOR / REVIEWER

Raymond P. Najjar