Digging Deeper for the Eye Proteome in Vitreous Substructures: A High-Resolution Proteome Map of the Normal Human Vitreous Base.

Mapping the normal eye proteome in healthy persons is essential to unravel the molecular basis of diseases impacting visual health. The vitreous occupies a large portion of the human eye between the lens and the retina and plays a significant role in vitreoretinal diseases as well as maintaining clarity in the visual field, providing nutrition to the lens, and protecting the eye from mechanical shocks. It comprises four distinct anatomical regions, namely the vitreous core, vitreous cortex, vitreous base, and anterior hyaloid. Among these, the vitreous is attached to other substructures in the eye by the vitreous base, which is its strongest point of attachment. Alterations in vitreous substructures have been reported in several vitreoretinal disorders, including vitreomacular traction, vitreoretinopathies, and age-related macular degeneration. There has been limited knowledge on proteomics variations at a resolution of vitreous substructures, including the functionally and pathophysiologically significant vitreous base. We report here new findings on the proteome map of the vitreous base in normal healthy tissue. We employed a global, unbiased proteomic profiling approach resulting in the identification of 6511 proteins. Of these, 302 proteins were involved in metabolic processes essential for energy utilization. Moreover, we identified several structural and nutrient transport proteins. Notably, the identified proteome repertoire indicates that the vitreous base might possess additional physiological functions and may not be a passive structure. This study constitutes the most extensive catalog of vitreous base proteins to our knowledge and offers novel insights as a baseline for future studies on the pathobiology of various eye diseases. These data also invite us to consider a potentially more active functional role for the vitreous base in eye physiology and visual health.

The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings.

An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.

Toward Postgenomics Ophthalmology: A Proteomic Map of the Human Choroid-Retinal Pigment Epithelium Tissue.

Ophthalmology and visual health research have received relatively limited attention from the personalized medicine community, but this trend is rapidly changing. Postgenomics technologies such as proteomics are being utilized to establish a baseline biological variation map of the human eye and related tissues. In this context, the choroid is the vascular layer situated between the outer sclera and the inner retina. The choroidal circulation serves the photoreceptors and retinal pigment epithelium (RPE). The RPE is a layer of cuboidal epithelial cells adjacent to the neurosensory retina and maintains the outer limit of the blood-retina barrier. Abnormal changes in choroid-RPE layers have been associated with age-related macular degeneration. We report here the proteome of the healthy human choroid-RPE complex, using reverse phase liquid chromatography and mass spectrometry-based proteomics. A total of 5309 nonredundant proteins were identified. Functional analysis of the identified proteins further pointed to molecular targets related to protein metabolism, regulation of nucleic acid metabolism, transport, cell growth, and/or maintenance and immune response. The top canonical pathways in which the choroid proteins participated were integrin signaling, mitochondrial dysfunction, regulation of eIF4 and p70S6K signaling, and clathrin-mediated endocytosis signaling. This study illustrates the largest number of proteins identified in human choroid-RPE complex to date and might serve as a valuable resource for future investigations and biomarker discovery in support of postgenomics ophthalmology and precision medicine.

A Comprehensive Proteomics Analysis of the Human Iris Tissue: Ready to Embrace Postgenomics Precision Medicine in Ophthalmology?

The annual economic burden of visual disorders in the United States was estimated at $139 billion. Ophthalmology is therefore one of the salient application fields of postgenomics biotechnologies such as proteomics in the pursuit of global precision medicine. Interestingly, the protein composition of the human iris tissue still remains largely unexplored. In this context, the uveal tract constitutes the vascular middle coat of the eye and is formed by the choroid, ciliary body, and iris. The iris forms the anterior most part of the uvea. It is a thin muscular diaphragm with a central perforation called pupil. Inflammation of the uvea is termed uveitis and causes reduced vision or blindness. However, the pathogenesis of the spectrum of diseases causing uveitis is still not very well understood. We investigated the proteome of the iris tissue harvested from healthy donor eyes that were enucleated within 6 h of death using high-resolution Fourier transform mass spectrometry. A total of 4959 nonredundant proteins were identified in the human iris, which included proteins involved in signaling, cell communication, metabolism, immune response, and transport. This study is the first attempt to comprehensively profile the global proteome of the human iris tissue and, thus, offers the potential to facilitate biomedical research into pathological diseases of the uvea such as Behcet's disease, Vogt Koyonagi Harada's disease, and juvenile rheumatoid arthritis. Finally, we make a call to the broader visual health and ophthalmology community that proteomics offers a veritable prospect to obtain a systems scale, functional, and dynamic picture of the eye tissue in health and disease. This knowledge is ultimately pertinent for precision medicine diagnostics and therapeutics innovation to address the pressing needs of the 21st century visual health.