Nadia K. Waheed , Richard B. Rosen , Yali Jia , Marion R. Munk , David Huang , Amani Fawzi , Victor Chong , Quan Dong Nguyen , Yasir Sepah , Elizabeth Pearce
{"title":"Optical coherence tomography angiography in diabetic retinopathy","authors":"Nadia K. Waheed , Richard B. Rosen , Yali Jia , Marion R. Munk , David Huang , Amani Fawzi , Victor Chong , Quan Dong Nguyen , Yasir Sepah , Elizabeth Pearce","doi":"10.1016/j.preteyeres.2023.101206","DOIUrl":"10.1016/j.preteyeres.2023.101206","url":null,"abstract":"<div><p>There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications.</p><p>A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies.</p><p>Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"97 ","pages":"Article 101206"},"PeriodicalIF":17.8,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10083731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ikhwanuliman Putera , Benjamin Schrijver , Josianne C.E.M. ten Berge , Vishali Gupta , Rina La Distia Nora , Rupesh Agrawal , P. Martin van Hagen , Saskia M. Rombach , Willem A. Dik
{"title":"The immune response in tubercular uveitis and its implications for treatment: From anti-tubercular treatment to host-directed therapies","authors":"Ikhwanuliman Putera , Benjamin Schrijver , Josianne C.E.M. ten Berge , Vishali Gupta , Rina La Distia Nora , Rupesh Agrawal , P. Martin van Hagen , Saskia M. Rombach , Willem A. Dik","doi":"10.1016/j.preteyeres.2023.101189","DOIUrl":"10.1016/j.preteyeres.2023.101189","url":null,"abstract":"<div><p>Tubercular uveitis (TB-uveitis) remains a conundrum in the uveitis field, which is mainly related to the diverse clinical phenotypes of TB-uveitis. Moreover, it remains difficult to differentiate whether <em>Mycobacterium tuberculosis</em> (<em>Mtb</em>) is present in the ocular tissues, elicits a heightened immune response without <em>Mtb</em> invasion in ocular tissues, or even induces an anti-retinal autoimmune response. Gaps in the immuno-pathological knowledge of TB-uveitis likely delay timely diagnosis and appropriate management. In the last decade, the immunopathophysiology of TB-uveitis and its clinical management, including experts' consensus to treat or not to treat certain conditions with anti-tubercular treatment (ATT), have been extensively investigated. In the meantime, research on TB treatment, in general, is shifting more toward host-directed therapies (HDT). Given the complexities of the host-<em>Mtb</em> interaction, enhancement of the host immune response is expected to boost the effectiveness of ATT and help overcome the rising burden of drug-resistant <em>Mtb</em> strains in the population. This review will summarize the current knowledge on the immunopathophysiology of TB-uveitis and recent advances in treatment modalities and outcomes of TB-uveitis, capturing results gathered from high- and low-burden TB countries with ATT as the mainstay of treatment. Moreover, we outline the recent progress of HDT development in the pulmonary TB field and discuss the possibility of its applicability to TB-uveitis. The concept of HDT might help direct future development of efficacious therapy for TB-uveitis, although more in-depth research on the immunoregulation of this disease is still necessary.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101189"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10152847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell identity changes in ocular surface Epithelia","authors":"Nick Di Girolamo, Mijeong Park","doi":"10.1016/j.preteyeres.2022.101148","DOIUrl":"10.1016/j.preteyeres.2022.101148","url":null,"abstract":"<div><p>Corneal and conjunctival epithelia arise from a common ancestral ectoderm cell, then diverge into distinct lineages. The former develops into a multilayered stratified squamous epithelium, the latter into an expansive mucous membrane that stretches the eyelid margin to the cornea's outskirts. The limbus, which intersects these epithelia, is purported to harbor corneal stem cells. Intrinsic programs that prevent these neighbouring epithelia from mixing and changing identity have not been elucidated, however microenvironmental cues that emanate following tissue damage and ensuing disease, dictate cell fate choices including those that influence form and function. Plasticity of ocular surface epithelia is gauged by their ability to undergo epithelial-mesenchymal transition, transdifferentiation, dedifferentiation and metaplastic transformation. Elucidating the molecular mechanism by which these rare and unusual phenomena arise, and persuading cells to either revert to their original state or remain newly committed, could be exploited into game-changing therapeutics for patients with corneal blindness and other diseases.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101148"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10161697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emily G. Saccuzzo, Hannah A. Youngblood, Raquel L. Lieberman
{"title":"Myocilin misfolding and glaucoma: A 20-year update","authors":"Emily G. Saccuzzo, Hannah A. Youngblood, Raquel L. Lieberman","doi":"10.1016/j.preteyeres.2023.101188","DOIUrl":"10.1016/j.preteyeres.2023.101188","url":null,"abstract":"<div><p>Mutations in the gene <span><em>MYOC</em></span><span> account for approximately 5% of cases of primary open angle glaucoma (POAG). </span><em>MYOC</em><span><span><span> encodes for the protein myocilin, a multimeric secreted glycoprotein composed of N-terminal coiled-coil (CC) and </span>leucine zipper<span><span><span> (LZ) domains that are connected via a disordered linker to a 30 kDa olfactomedin (OLF) domain. More than 90% of glaucoma-causing mutations are localized to the OLF domain. While myocilin is expressed in numerous tissues, mutant myocilin is only associated with disease in the anterior segment of the eye, in the trabecular meshwork. The prevailing pathogenic mechanism involves a gain of toxic function whereby mutant myocilin aggregates intracellularly instead of being secreted, which causes cell stress and an early timeline for TM </span>cell death, elevated </span>intraocular pressure, and subsequent glaucoma-associated </span></span>retinal degeneration. In this review, we focus on the work our lab has conducted over the past ∼15 years to enhance our molecular understanding of myocilin-associated glaucoma, which includes details of the molecular structure and the nature of the aggregates formed by mutant myocilin. We conclude by discussing open questions, such as predicting phenotype from genotype alone, the elusive native function of myocilin, and translational directions enabled by our work.</span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101188"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10330797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9794571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruchi Shah , Cynthia Amador , Steven T. Chun , Sean Ghiam , Mehrnoosh Saghizadeh , Andrei A. Kramerov , Alexander V. Ljubimov
{"title":"Non-canonical Wnt signaling in the eye","authors":"Ruchi Shah , Cynthia Amador , Steven T. Chun , Sean Ghiam , Mehrnoosh Saghizadeh , Andrei A. Kramerov , Alexander V. Ljubimov","doi":"10.1016/j.preteyeres.2022.101149","DOIUrl":"10.1016/j.preteyeres.2022.101149","url":null,"abstract":"<div><p>Wnt signaling comprises a group of complex signal transduction pathways that play critical roles in cell proliferation, differentiation, and apoptosis during development, as well as in stem cell maintenance and adult tissue homeostasis. Wnt pathways are classified into two major groups, canonical (β-catenin-dependent) or non-canonical (β-catenin-independent). Most previous studies in the eye have focused on canonical Wnt signaling, and the role of non-canonical signaling remains poorly understood. Additionally, the crosstalk between canonical and non-canonical Wnt signaling in the eye has hardly been explored. In this review, we present an overview of available data on ocular non-canonical Wnt signaling, including developmental and functional aspects in different eye compartments. We also discuss important changes of this signaling in various ocular conditions, such as keratoconus, aniridia-related keratopathy, diabetes, age-related macular degeneration, optic nerve damage, pathological angiogenesis, and abnormalities in the trabecular meshwork and conjunctival cells, and limbal stem cell deficiency.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101149"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10209355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Won-Kyu Ju , Guy A. Perkins , Keun-Young Kim , Tonking Bastola , Woo-Young Choi , Soo-Ho Choi
{"title":"Glaucomatous optic neuropathy: Mitochondrial dynamics, dysfunction and protection in retinal ganglion cells","authors":"Won-Kyu Ju , Guy A. Perkins , Keun-Young Kim , Tonking Bastola , Woo-Young Choi , Soo-Ho Choi","doi":"10.1016/j.preteyeres.2022.101136","DOIUrl":"10.1016/j.preteyeres.2022.101136","url":null,"abstract":"<div><p>Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by a slow, progressive, and multifactorial degeneration of retinal ganglion cells (RGCs) and their axons, resulting in vision loss. Despite its high prevalence in individuals 60 years of age and older, the causing factors contributing to glaucoma progression are currently not well characterized. Intraocular pressure (IOP) is the only proven treatable risk factor. However, lowering IOP is insufficient for preventing disease progression. One of the significant interests in glaucoma pathogenesis is understanding the structural and functional impairment of mitochondria in RGCs and their axons and synapses. Glaucomatous risk factors such as IOP elevation, aging, genetic variation, neuroinflammation, neurotrophic factor deprivation, and vascular dysregulation, are potential inducers for mitochondrial dysfunction in glaucoma. Because oxidative phosphorylation stress-mediated mitochondrial dysfunction is associated with structural and functional impairment of mitochondria in glaucomatous RGCs, understanding the underlying mechanisms and relationship between structural and functional alterations in mitochondria would be beneficial to developing mitochondria-related neuroprotection in RGCs and their axons and synapses against glaucomatous neurodegeneration. Here, we review the current studies focusing on mitochondrial dynamics-based structural and functional alterations in the mitochondria of glaucomatous RGCs and therapeutic strategies to protect RGCs against glaucomatous neurodegeneration.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101136"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mirella Telles Salgueiro Barboni , Anneka Joachimsthaler , Michel J. Roux , Zoltán Zsolt Nagy , Dora Fix Ventura , Alvaro Rendon , Jan Kremers , Cyrille Vaillend
{"title":"Retinal dystrophins and the retinopathy of Duchenne muscular dystrophy","authors":"Mirella Telles Salgueiro Barboni , Anneka Joachimsthaler , Michel J. Roux , Zoltán Zsolt Nagy , Dora Fix Ventura , Alvaro Rendon , Jan Kremers , Cyrille Vaillend","doi":"10.1016/j.preteyeres.2022.101137","DOIUrl":"10.1016/j.preteyeres.2022.101137","url":null,"abstract":"<div><p>Duchenne muscular dystrophy (DMD) is caused by X-linked inherited or <em>de novo DMD</em> gene mutations predominantly affecting males who develop early-onset muscle degeneration, severely affecting their quality of life and leading to reduced life expectancy. DMD patients may also develop proliferative retinopathy, cataract, ERG abnormalities, altered contrast sensitivity, color vision losses, and elevated flash detection thresholds during dark adaptation. Depending on the position of the genetic alteration in the large <em>DMD</em> gene, it is associated with a lack of the full-length dystrophin protein possibly with an additional loss of one or several other dystrophins, which are normally transcribed from internal promoters in retina and crystalline lens. During the last decades, the properties of the dystrophins have been characterized in patients with different genetic alterations and in genetic mouse models of DMD. The complex expression pattern of the dystrophins in photoreceptors, Müller glial cells and astrocytes, likely influences synaptic transmission, ionic balance and vascular integrity of the retina. However, the specific function of each retinal dystrophin remains largely unknown. This review describes the current knowledge on dystrophin expression, the putative molecular, structural, and physiological properties of retinal dystrophins, and the main clinical implications associated with the loss of dystrophins in DMD patients and mouse models. Current data and working hypotheses warrant future research on retinal dystrophins to increase our understanding of dystrophin function in the central nervous system in general and to unveil new retinal mechanisms and therapeutic avenues for retinal diseases.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101137"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Secondary outcomes of lens and cataract surgery: More than just “best-corrected visual acuity”","authors":"Idan Hecht , Piotr Kanclerz , Raimo Tuuminen","doi":"10.1016/j.preteyeres.2022.101150","DOIUrl":"10.1016/j.preteyeres.2022.101150","url":null,"abstract":"<div><p>Most studies evaluating cataract surgery focus on the primary outcome of early, central, best-corrected visual acuity. However, cataract surgery and intraocular lens (IOL) design have other secondary visual outcomes as well as impacts on various ocular tissues, the visual function, and quality of life. Some of these aspects are more difficult to quantify, or are historically neglected, but might be extremely important to patients. One important development was the addition of blue-light filtering to IOL design. Whether these IOLs truly have the retinal protective qualities they were designed for is disputed, yet other inadvertent desirable and possibly detrimental influences are being examined. Risk of falls, driving accidents, and other injuries decrease following cataract surgery, especially in the elderly, the importance of which cannot be overemphasized. Cataract formation contributes to social isolation and decreases cognitive stimulation in the elderly population, while cataract extraction can reduce the risk of dementia and cognitive decline. Diffractive multifocal and extended depth-of-focus IOLs improve spectacle independence and patient reported outcomes, but positive and negative dysphotopsia may be persistent. Future directions such as using the IOL enabling clear spectacle-free vision at all distances, or intraoperative drug delivery systems show promising preliminary results. It seems inevitable that a higher focus on the secondary outcomes of surgery will increase. We believe that these aspects will become more and more relevant when considering new IOL designs and surgical techniques, a fact that will benefit both the patients and the surgeons.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101150"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9776609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alejandra Daruich , Melinda Duncan , Matthieu P. Robert , Neil Lagali , Elena V. Semina , Daniel Aberdam , Stefano Ferrari , Vito Romano , Cyril Burin des Roziers , Rabia Benkortebi , Nathalie De Vergnes , Michel Polak , Frederic Chiambaretta , Ken K. Nischal , Francine Behar-Cohen , Sophie Valleix , Dominique Bremond-Gignac
{"title":"Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches","authors":"Alejandra Daruich , Melinda Duncan , Matthieu P. Robert , Neil Lagali , Elena V. Semina , Daniel Aberdam , Stefano Ferrari , Vito Romano , Cyril Burin des Roziers , Rabia Benkortebi , Nathalie De Vergnes , Michel Polak , Frederic Chiambaretta , Ken K. Nischal , Francine Behar-Cohen , Sophie Valleix , Dominique Bremond-Gignac","doi":"10.1016/j.preteyeres.2022.101133","DOIUrl":"10.1016/j.preteyeres.2022.101133","url":null,"abstract":"<div><p>Congenital <em>PAX6</em>-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities and systemic features making congenital aniridia a complex syndromic disorder rather than a simple isolated disease of the iris. Moreover, foveal hypoplasia is now recognized as a more frequent feature than complete iris hypoplasia and a major visual prognosis determinant, reversing the classical clinical picture of this disease. Conversely, iris malformation is also a feature of various anterior segment dysgenesis disorders caused by <em>PAX6</em>-related developmental genes, adding a level of genetic complexity for accurate molecular diagnosis of aniridia. Therefore, the clinical recognition and differential genetic diagnosis of <em>PAX6</em>-related aniridia has been revealed to be much more challenging than initially thought, and still remains under-investigated.</p><p>Here, we update specific clinical features of aniridia, with emphasis on their genotype correlations, as well as provide new knowledge regarding the <em>PAX6</em> gene and its mutational spectrum, and highlight the beneficial utility of clinically implementing targeted Next-Generation Sequencing combined with Whole-Genome Sequencing to increase the genetic diagnostic yield of aniridia. We also present new molecular mechanisms underlying aniridia and aniridia-like phenotypes. Finally, we discuss the appropriate medical and surgical management of aniridic eyes, as well as innovative therapeutic options.</p><p>Altogether, these combined clinical-genetic approaches will help to accelerate time to diagnosis, provide better determination of the disease prognosis and management, and confirm eligibility for future clinical trials or genetic-specific therapies.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101133"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9785340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul J. Donaldson, Yadi Chen, Rosica S. Petrova, Angus C. Grey, Julie C. Lim
{"title":"Regulation of lens water content: Effects on the physiological optics of the lens","authors":"Paul J. Donaldson, Yadi Chen, Rosica S. Petrova, Angus C. Grey, Julie C. Lim","doi":"10.1016/j.preteyeres.2022.101152","DOIUrl":"10.1016/j.preteyeres.2022.101152","url":null,"abstract":"<div><p><span>The lens is an important determinant of overall vision quality whose refractive and transparent properties change throughout life. Alterations to the refractive properties of the lens contribute to the process of emmetropisation<span> in early childhood, and then the gradual loss in lens power that occurs throughout adulthood. In parallel to these changes to lens refractive power, age-dependent increases in lens stiffness and light scattering result in presbyopia<span><span> and cataract, respectively. In recent years it has been confirmed that the lens operates an internal microcirculation system that generates circulating fluxes of ions, water and nutrients that maintain the refractive properties and transparency of the lens. By actively regulating lens water content, the microcirculation system controls two key parameters, lens geometry and the gradient of refractive index, which together determine the refractive properties of the lens. Furthermore, by delivering nutrients and antioxidants to the </span>lens nucleus<span>, the microcirculation system maintains lens transparency by preventing crystallin aggregation. Interestingly, the solubility, intramolecular packing and refractive index increment of crystallin proteins can be modulated by the ability of crystallin proteins to dynamically bind water, a processed called syneresis. In a series of previous studies it has been shown that the application of external pressure to the lens can induce syneresis. Since it is now known that lens water transport generates a substantial internal hydrostatic pressure gradient, we speculate that the microcirculation is capable of regulating crystallin function by altering the amount of water bound to </span></span></span></span>lens proteins in the nucleus, where the pressure gradient and protein concentrations are the highest. Here we present evidence for the links between lens transport, pressure, syneresis and protein function. Furthermore, because the lens pressure gradient can be regulated by intrinsic and extrinsic stimuli, we suggest mechanisms via which this integrative system can be used to effect the changes to the refractive and transparent properties of the lens that are observed across our lifetime.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101152"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10162176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}