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Myopia, or short-sightedness, is a highly prevalent refractive disorder in which the eye’s focal length is too short for its axial dimension in its relaxed state. High myopia is associated with increased risks of blinding ocular complications and abnormal eye shape. In addition to consistent findings on posterior segment anomalies in high myopia (e.g., scleral remodeling), more recent biometric and biomechanical data in myopic humans and animal models also indicate anterior segment anomalies (e.g., corneal biomechanical properties). Because the cornea is the anterior-most ocular tissue, providing essential refractive power and physiological stability, it is important to understand the biochemical signaling pathway during myopia development. This study first aimed to establish the entire chicken corneal proteome. Then, using the classical form deprivation paradigm to induce high myopia in chicks, state-of-the-art bioinformatics technologies were applied to identify eight differentially expressed proteins in the highly myopic cornea. These results provide strong foundation for future corneal research, especially those using chicken as an animal model for myopia development.

Background Mice are an emerging model for experimental myopia. Due to their small eye size, non-invasive optical coherence tomography is essential for evaluating ocular biometrics. There is currently no universally accepted protocol for those measurements. This study aims to compare ocular biometric measurements using two methods: Purkinje image-based alignment and optic nerve head alignment, utilizing spectral domain optical coherence tomography. Gaining an understanding of the implications of these methods in determining axial elongation in the normal growing eyes of wild-type C57BL/6J mice would offer valuable insight into their relevance for the experimental myopia model. Methods Ocular dimensions and refractive development were measured on postnatal days P21 (n = 10), P28 (n = 15), and P35 (n = 8). The Purkinje image-based alignment (P1) was determined using a photorefractor and aligned perpendicular to the corneal apex using SD-OCT. In comparison, due to the absence of a fovea in the mouse retina, the optic nerve head (ONH) alignment was used. Variance analysis, regression analysis, and Bland–Altman analysis were performed to compare the differences between alignment methods as well as the replication by another operator. Results Mice developed hyperopic ametropia under normal visual conditions. The photorefractor measured a technical variation of 3.9 D (95% CI, n = 170, triplicates). Bland–Altman analysis revealed a shorter (mean ± SD) axial length (− 26.4 ± 18.1 μm) and vitreous chamber depth (− 39.9 ± 25.4 μm) in the Purkinje image-based alignment. There was a significant difference in the relative growth trend in VCD (linear regression, p = 0.02), which was relatively stable and showed shortening when measured with ONH alignment from postnatal age 21 to 35 days. Conclusions SD-OCT allowed precise in-vivo measurement and segmentation of ocular dimensions, regardless of the methods adopted. P1 alignment consistently resulted in significantly shorter VCD and AL compared to ONH alignment at most time points. When considering temporal changes from P21 to P35, both methods showed similar results, with significant elongation of ACD, LT, and AL as expected. However, our findings revealed a significant shortening of VCD over time with the adoption of ONH alignment, while the change in P1 alignment was relatively stable. Therefore, AL provides a better measure for evaluating ocular growth in mice using optical coherence tomography than VCD for myopia research.

Background: Glaucoma requires therapies that extend beyond intraocular pressure (IOP)-lowering strategies, and baicalein (BA) offers dual IOP-lowering and neuroprotective potential. This study evaluated the pharmacokinetics of BA and its major metabolite baicalin (BG) in mouse eyes and serum after intravitreal (IVT) and oral administration to determine whether non-invasive oral dosing can achieve IVT-comparable ocular exposure. Methods: BA was administered via IVT injection (100 μM) or oral gavage (20 and 200 mg/kg) in mice, and concentrations of BA and BG in serum and ocular tissues were quantified using a validated ultra-performance liquid chromatography–mass spectrometry (UHPLC/MS) method. Results: After IVT, ocular BA peaked at 331.56 ± 17.75 ng/g at 5 min and declined to 7.13 ± 0.79 ng/g at 4 h, with minimal systemic exposure. Oral administration achieved comparable or higher peak ocular BA levels (380.43 ± 52.85 ng/g at 15 min for 20 mg/kg; 309.70 ± 24.75 ng/g at 5 min for 200 mg/kg), with markedly higher ocular area under the concentration–time curve (AUC: 2455.48 ± 667.83 h·ng/g for 200 mg/kg and 1224.88 ± 751.13 h·ng/g for 20 mg/kg) versus IVT (247.07 h·ng/g). Serum BA and BG peaked at 5 min after oral dosing, with systemic BG exposure substantially exceeding BA. Conclusions: Non-invasive oral BA dosing achieves ocular concentrations comparable to IVT injection, with significantly greater overall exposure and favorable pharmacokinetic profiles. This study provides the first demonstration in mice that non-invasive oral BA administration can replace invasive IVT delivery, establishing a strong rationale for its clinical development in glaucoma and retinal disease management.

Purpose: Atropine, a non-selective muscarinic antagonist, effectively slows down myopia progression in human adolescents and several animal models. However, the underlying molecular mechanism is unclear. The current study investigated retinal protein changes of form-deprived myopic (FDM) guinea pigs in response to topical administration of 1% atropine gel (10 g/L). Methods: At the first stage, the differentially expressed proteins were screened using fractionated isobaric tags for a relative and absolute quantification (iTRAQ) approach, coupled with nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) ( n = 24, 48 eyes) using a sample pooling technique. At the second stage, retinal tissues from another cohort with the same treatment ( n = 12, 24 eyes) with significant ocular changes were subjected to label-free sequential window acquisition of all theoretical mass spectra (SWATH-MS) proteomics for orthogonal protein target confirmation. The localization of Alpha-synuclein was verified using immunohistochemistry and confocal imaging. Results: A total of 1,695 proteins (8,875 peptides) were identified with 479 regulated proteins (FC ≥ 1.5 or ≤0.67) found from FDM eyes and atropine-treated eyes receiving 4-weeks drug treatment using iTRAQ-MS proteomics. Combining the iTRAQ-MS and SWATH-MS datasets, a total of 29 confident proteins at 1% FDR were consistently quantified and matched, comprising 12 up-regulated and 17 down-regulated proteins which differed between FDM eyes and atropine treated eyes (iTRAQ: FC ≥ 1.5 or ≤0.67, SWATH: FC ≥ 1.4 or ≤0.71, p -value of ≤0.05). Bioinformatics analysis using IPA and STRING databases of these commonly regulated proteins revealed the involvement of the three commonly significant pathways: EIF2 signaling; glycolysis; and dopamine secretion. Additionally, the most significantly regulated proteins were closely connected to Alpha-synuclein (SNCA). Using immunostaining ( n = 3), SNCA was further confirmed in the inner margin of the inner nuclear layer (INL) and spread throughout the inner plexiform layer (IPL) of the retina of guinea pigs. Conclusion: The molecular evidence using next-generation proteomics (NGP) revealed that retinal EIF2 signaling, glycolysis, and dopamine secretion through SNCA are implicated in atropine treatment of myopia in the FDM-induced guinea pig model.

Myopia is increasingly prevalent worldwide, with projections indicating that nearly 50% of the global population may have myopia by 2050. This surge poses significant concerns due to its impact on vision and quality of life and its link to a range of blinding diseases, including myopic macular degeneration, glaucoma, and retinal detachment. Current pharmacologic and optical interventions offer limited effectiveness in slowing myopia progression, highlighting the urgent need for more effective treatments. This study aims to examine the combined effect of bright light therapy and low-dose atropine on myopic progression. This is a single-site, 2-arm, single-masked (examiner-masked) randomized controlled trial to compare the effectiveness of low-dose atropine alone and its combination with bright light therapy in retarding myopia progression. The study protocol has been approved by the institutional review boards of Hong Kong Polytechnic University (HSEARS 20180829002-05) and the University of Hong Kong and Hospital Authority Hong Kong West Cluster (UW 20-362). Schoolchildren with myopia aged 7 to 12 years who have not undergone any previous myopic control intervention will be recruited and randomly allocated into 2 groups (n=67 per group) after baseline measurements. Both groups will receive 0.01% atropine twice daily for 24 months. The combination treatment group will also receive a high-intensity lamp for bright light therapy. The primary and secondary outcome measures will be the changes in cycloplegic autorefraction in spherical equivalent refraction and axial length, respectively, measured every 6 months over 2 years from baseline. The project was funded in January 2019. The recruitment process started on March 21, 2023, and was completed on February 2, 2024. Data collection is expected to be completed in April 2026. This study will provide new information on whether the combination of bright light therapy and low-dose atropine is more effective than atropine alone in slowing down myopia progression. It will also assess the effectiveness of low-dose atropine used twice daily. Combining bright light therapy and atropine could become a new treatment option if shown to be effective. New data on the effectiveness of using atropine twice daily might also expand available treatment options.

The corneal epithelium serves as the front barrier against environmental stimuli and pathogens on the ocular surface. A comprehensive protein profile of the corneal epithelium would be crucial for understanding the molecular mechanisms that are related to corneal disease. This work demonstrated a library-free data-independent acquisition (DIA) approach across different mass spectrometers and proteomic software to build a comprehensive proteomic dataset for human corneal epithelial cells (HCECs). With the combinational use of different data-independent acquisition technologies of multiple mass spectrometers, including Sciex ZenoTOF 7600 (DIA-SWATH), Bruker TimsTOF Pro2 (DIA-PASEF), and ThermoFisher Orbitrap Fusion Lumos (DIA-HRMS1), protein identification and quantification were performed with superior sensitivity and resolution. By using a library-free DIA approach, this study constructed a more diverse and unbiased proteomic profile of human corneal epithelial cells (HCECs), comprising 11,954 protein groups (1% FDR). This represents the largest corneal proteome reported to date. All raw proteomic data were deposited to ProteomeXchange Consortium via Proteomics Identifications database (PRIDE) with the dataset identifier accession number PXD059451. Our findings hold the potential to enhance future understanding of corneal pathologies and transformative therapeutics.

Low-dose atropine helps to control myopia progression with few side effects. However, the impact of atropine, a non-selective muscarinic Acetylcholine (ACh) receptor antagonist, on retinal ganglion cells (RGCs) remains unclear. After immersing the cornea and adjacent conjunctiva of enucleated eyes in 0.05% (approximately 800 μM) atropine solution for 30 min, the atropine concentration reached in the retina was below 2 μM. After direct superfusion of the retina with 1 μM atropine (considering that the clinical application of 0.05% atropine eye drops will be diluted over time due to tear flow for 30 min), no noticeable changes in the morphology of ON and OFF alpha RGCs (αRGCs) were observed. Atropine affected the light-evoked responses of ON and OFF αRGCs in a dose- and time-dependent fashion. Direct application of less than 100 μM atropine on the retina did not affect light-evoked responses. The time latency of light-induced responses of ON or OFF αRGCs did not change after the application of 0.05–100 μM atropine for 5 min. However, 50 μM atropine extended the threshold of joint inter-spike interval (ISI) distribution of the RGCs. These results indicated that low-dose atropine (<0.5 μM; equal to 1% atropine topical application) did not interfere with spike frequency, the pattern of synchronized firing between OFF αRGCs, or the threshold of joint ISI distribution of αRGCs. The application of atropine unmasked inhibition to induce ON responses from certain OFF RGCs, possibly via the GABAergic pathway, potentially affecting visual information processing.

Background In the past decade and during the COVID pandemic, the prevalence of myopia has reached epidemic proportions. To address this issue and reduce the prevalence of myopia and its complications, it is necessary to develop more effective interventions for controlling myopia. In this study, we investigated the combined effects of narrowband lights and competing defocus on eye growth and refraction in chicks, an important step in understanding the potential for these interventions to control myopia. This is the first time these effects have been characterized. Methods Three groups of five-day-old chicks (n = 8 per group) were raised in three different lighting conditions: white, red, and blue for 13 days in a 12/12-h light/dark diurnal cycle. One eye was randomly selected for applications of a dual-power optical lens (− 10 D/ + 10 D, 50∶50), while another eye was left untreated as control. Vitreous chamber depth (VCD), axial length (AL), choroidal thickness (CT) and refractive errors were measured at pre-exposure (D0) and following 3 (D3), 7 (D7), 10 (D10), and 13 days (D13) of light exposure. Results Under white light, the dual-power lens induced a hyperopic shift [at D13, mean spherical equivalent refraction (SER), treated vs. control: 4.81 ± 0.43 D vs. 1.77 ± 0.21 D, P  < 0.001] and significantly reduced the progression of axial elongation (at D13, change in AL, treated vs. control: 1.25 ± 0.04 mm vs. 1.45 ± 0.05 mm, P  < 0.01). Compared to white light alone, blue light alone induced a hyperopic shift (at D13, mean SER, blue vs. white: 2.75 ± 0.21 D vs. 1.77 ± 0.21 D, P  < 0.01) and significantly reduced axial elongation (at D13, change in AL, blue vs. white: 1.17 ± 0.06 mm vs. 1.45 ± 0.05 mm, P  < 0.01) in control eyes. When comparing all conditions, eyes exposed to blue light plus dual-power lens had the least axial elongation (at D13, change in AL, 0.99 ± 0.05 mm) and were the most hyperopic (at D13, mean SER, 6.36 ± 0.39 D). Conclusions Both narrowband blue light and dual-power lens interventions were effective in inducing a hyperopic shift in chicks, and provided protection against myopia development. The combination of these interventions had additive effects, making them potentially even more effective. These findings support the use of optical defocus interventions in combination with wavelength filters in clinical studies testing their effectiveness in treating myopia in children.

Age-related macular degeneration (AMD) is a degenerative eye disease leading to central vision loss and is characterized by dysregulated autophagy of the retinal pigment epithelium (RPE) layer. Recent studies have suggested that rho-associated protein kinase (ROCK) inhibitors may enhance autophagy in neurodegenerative diseases and promote the survival of RPE cells. This study investigated the effect of ROCK inhibitors on autophagy gene expression and autophagic vacuole formation in a human RPE (ARPE-19) cell line. The highly selective and potent ROCK inhibitor Y-39983 enhanced the expression of autophagy genes in ARPE-19 cells and increased autophagic vacuole formation. A proteomic analysis using mass spectrometry was performed to further characterize the effects of ROCK inhibition at the protein level. Y-39983 downregulated thrombospondin-1 (THBS1), and suppression of THBS1 in ARPE-19 cells resulted in an increase in autophagic vacuole formation. Our data showed that ROCK inhibitor-induced autophagy was mediated by THBS1 downregulation. We identified ROCK and THBS1 as potential novel therapeutic targets in AMD.

The retina is a key sensory tissue composed of multiple layers of cell populations that work coherently to process and decode visual information. Mass spectrometry-based proteomics approach has allowed high-throughput, untargeted protein identification, demonstrating the presence of these proteins in the retina and their involvement in biological signalling cascades. The comprehensive wild-type mouse retina proteome was prepared using a novel sample preparation approach, the suspension trapping (S-Trap) filter, and further fractionated with high-pH reversed phase chromatography involving a total of 28 injections. This data-dependent acquisition (DDA) approach using a Sciex TripleTOF 6600 mass spectrometer identified a total of 7,122 unique proteins (1% FDR), and generated a spectral library of 5,950 proteins in the normal C57BL/6 mouse retina. Data-independent acquisition (DIA) approach relies on a large and high-quality spectral library to analyse chromatograms, this spectral library would enable access to SWATH-MS acquisition to provide unbiased, multiplexed, and quantification of proteins in the mouse retina, acting as the most extensive reference library to investigate retinal diseases using the C57BL/6 mouse model. Measurement(s) retina Technology Type(s) mass spectrometry Sample Characteristic - Organism Mus musculus Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.13128044