Intraocular pressure is a promising target for myopia control

Abstract

Background: Myopia presents a noteworthy global health concern, urging exploration of innovative treatments. The role of intraocular pressure (IOP) in regulating the progression of myopia has been controversial.

Methods: To investigate the impact of reducing IOP to varying extents on myopia progression, three groups receiving distinct IOP-lowering medications (Brinzolamide, Latanoprost, and a combination of Brinzolamide and Latanoprost) were designed in a form-deprived myopic guinea pig model. Additionally, proteomics analyses were conducted to identify differentially expressed proteins in the sclera.

Results: Based on 24-h and 4-week IOP monitoring, the group receiving both Brinzolamide and Latanoprost exhibited the greatest magnitude of IOP reduction and the most significant inhibition of axial length (AL) growth. Moreover, the administration of IOP-lowering medications increased choroidal thickness and induced alterations in the structure of scleral collagen fibrils. Notably, scleral proteomics revealed remodeling processes associated with key mechanisms, including proteolysis, fibrinolysis, and metal ion binding.

Conclusions: Our findings highlight that pressure-dependent scleral remodeling contributes to the deceleration of AL elongation. These results underscore the efficacy of IOP reduction in mitigating the progression of myopia, providing a promising alternative strategy for myopia management.

Keywords: Axial elongation; IOP-lowering medication; Intraocular pressure; Myopia; Proteomics; Sclera remodeling.

Fig. 1

Effect of various IOP-lowering agents on myopia progression in guinea pigs. a 24-h intraocular pressure (IOP) fluctuations in the form-deprived group and three other groups receiving distinct IOP-lowering treatments. Green and red arrows indicate the time points for application of Latanoprost or Brinzolamide eye drops, respectively. b Violin plot depicting the range of 24-h IOP profiles across the four groups. c Weekly IOP measurements conducted in the right eyes of guinea pigs during four consecutive weeks. d Weekly increases in axial length (AL) compared among the four groups. e Analysis of interocular differences in AL changes across the four groups. f Changes in spherical equivalent (SE) observed among the four groups during the four-week period. (ns, non-significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, n = 10 per group)

Fig. 2

Effect of various IOP-lowering agents on choroid and sclera changes. a Illustration of the analysis template for optical coherence tomography (OCT) image and representative structural OCT images were displayed. b Comparison of mean choroidal thickness among the five groups. c Transmission electron microscope images of scleral collagen fibrils and diameter distribution histograms of the middle scleral layer in the five groups. d Violin plot displaying diameters of scleral collagen fibrils among the five groups. (ns, non-significant, **p < 0.01, ****p < 0.0001)

Fig. 3

GO enrichment and KEGG pathway analysis of protein clusters based on different proteins and clustering. a Volcano plots illustrating differential proteins among various groups. b Heatmap displaying differential proteins across different groups. c Fuzzy c-means clustering of differential proteins. d GO enrichment analysis of differential proteins within Cluster 5. e GO enrichment analysis of differential proteins across Cluster 1, 3, and 4. f KEGG pathway analysis of differential proteins in Cluster 5. g KEGG pathway analysis highlighting differential proteins in Clusters 1, 3, and 4. (Proteins corresponding to GO and KEGG terms in the red-framed boxes were chosen for subgroup analysis)

Fig. 4

Overlapped proteins among differential protein profiles and select proteins. a The protein profiles of FDM_A vs FDM groups and FDM_B vs FDM groups, FDM_AB vs FDM groups and FDM_B vs FDM groups, FDM_A vs FDM groups and FDM_B vs FDM groups exhibited overlaps with 15, 18, and 19 differential proteins, respectively. A total of 14 proteins were found to be overlapped across all three profiles, and their details and fold changes are presented in the heatmap. b Relative quantitative values of selected labeled proteins

Fig. 5

Subgroup analysis of differential proteins within targeted GO and KEGG terms from clusters. a Heatmap depicting differential proteins associated with targeted GO and KEGG terms from Cluster 5 and Clusters 1, 3, and 4. b Relative quantitative values of select labeled proteins. c Protein–protein interaction (PPI) analysis of differential proteins linked to targeted GO and KEGG terms from Cluster 5. d PPI analysis of differential proteins linked to targeted GO and KEGG terms from Clusters 1, 3, and 4