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Progress in Retinal and Eye Research Jul 2023Corneal and conjunctival epithelia arise from a common ancestral ectoderm cell, then diverge into distinct lineages. The former develops into a multilayered stratified... (Review)
Review
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.
Topics: Humans; Epithelium; Cornea; Cell Differentiation; Epithelium, Corneal; Conjunctiva
PubMed: 36418216
DOI: 10.1016/j.preteyeres.2022.101148 -
Survey of Ophthalmology 2023Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet... (Review)
Review
Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet membrane and endothelium. DMEK offers significant advantages over other keratoplasty techniques, such as faster visual rehabilitation, better final visual acuity due to minimal optical interface effects, lower risk of allograft rejection, and less long-term dependence on topical steroids. Despite all its advantages, DMEK has been found to be more challenging than other corneal transplantation techniques, and its steep learning curve appears to be an obstacle to its widespread use and adoption by corneal surgeons worldwide. DMEK surgical training laboratories (wet labs) provide a window of opportunity for surgeons to learn, prepare, manipulate, and deliver these grafts in a risk-free environment. Wet labs are a significant learning tool, especially for those institutions that have limited tissue availability in their local centers. We provide a step-by-step guide for preparing DMEK grafts using different techniques on human and nonhuman models with instructional videos. This article should eventually help the trainees and the educators understand the requirements for performing DMEK and conducting a DMEK wet lab and develop their skills and interests from a wide variety of available techniques.
Topics: Humans; Descemet Membrane; Laboratories; Descemet Stripping Endothelial Keratoplasty; Cornea; Endothelium, Corneal; Corneal Diseases
PubMed: 37392969
DOI: 10.1016/j.survophthal.2023.06.008 -
Translational Vision Science &... Jul 2023Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of...
Glaucomatous optic neuropathy (GON) is the major cause of irreversible visual loss worldwide and can result from a range of disease etiologies. The defining features of GON are retinal ganglion cell (RGC) degeneration and characteristic cupping of the optic nerve head (ONH) due to tissue remodeling, while intraocular pressure remains the only modifiable GON risk factor currently targeted by approved clinical treatment strategies. Efforts to understand the mechanisms that allow species such as the zebrafish to regenerate their retinal cells have greatly increased our understanding of regenerative signaling pathways. However, proper integration within the retina and projection to the brain by the newly regenerated neuronal cells remain major hurdles. Meanwhile, a range of methods for in vitro differentiation have been developed to derive retinal cells from a variety of cell sources, including embryonic and induced pluripotent stem cells. More recently, there has been growing interest in the implantation of glial cells as well as cell-derived products, including neurotrophins, microRNA, and extracellular vesicles, to provide functional support to vulnerable structures such as RGC axons and the ONH. These approaches offer the advantage of not relying upon the replacement of degenerated cells and potentially targeting earlier stages of disease pathogenesis. In order to translate these techniques into clinical practice, appropriate cell sourcing, robust differentiation protocols, and accurate implantation methods are crucial to the success of cell-based therapy in glaucoma. Translational Relevance: Cell-based therapies for glaucoma currently under active development include the induction of endogenous regeneration, implantation of exogenously derived retinal cells, and utilization of cell-derived products to provide functional support.
Topics: Animals; Zebrafish; Glaucoma; Optic Disk; Retina; Intraocular Pressure; Optic Nerve Diseases
PubMed: 37494052
DOI: 10.1167/tvst.12.7.23 -
Journal of Biomedical Optics Dec 2023The assessment of biomarkers in the eye is rapidly gaining traction for the screening, diagnosis, and monitoring of ocular and neurological diseases. Targeted ocular...
SIGNIFICANCE
The assessment of biomarkers in the eye is rapidly gaining traction for the screening, diagnosis, and monitoring of ocular and neurological diseases. Targeted ocular spectroscopy is a technology that enables concurrent imaging of the eye fundus and analysis of high-quality spectra from a targeted region within the imaged area. This provides structural, compositional, and functional information of specific regions of the eye fundus from a non-invasive approach to ocular biomarker detection.
AIM
The aim of our study was to demonstrate the multimodal functionality and validation of targeted ocular spectroscopy. This was done , using a reference target and a model eye, and .
APPROACH
Images and spectra from different regions of a reference target and a model eye were acquired and analyzed to validate the system. Targeted ocular fluorescence spectroscopy was also demonstrated with the same model. Subsequently, imaging and diffuse reflectance spectra were acquired to assess blood oxygen saturation in the optic nerve head and the parafovea of healthy subjects.
RESULTS
Tests conducted with the reference target showed accurate spectral analysis within specific areas of the imaging space. In the model eye, distinct spectral signatures were observed for the optic disc, blood vessels, the retina, and the macula, consistent with the variations in tissue composition and functions between these regions. An ocular oximetry algorithm was applied to spectra from the optic nerve head and parafovea of healthy patients, showing significant differences in blood oxygen saturation. Finally, targeted fluorescence spectral analysis was performed .
CONCLUSIONS
Diffuse reflectance and fluorescence spectroscopy in specific regions of the eye fundus open the door to a whole new range of monitoring and diagnostic capabilities, from assessment of oxygenation in glaucoma and diabetic retinopathy to photo-oxidation and photodegradation in age-related macular degeneration.
Topics: Humans; Fundus Oculi; Retina; Optic Disk; Oximetry; Spectrometry, Fluorescence
PubMed: 38111476
DOI: 10.1117/1.JBO.28.12.126004 -
Investigative Ophthalmology & Visual... Nov 2023To evaluate whether pigmented guinea pigs with spontaneous myopia present characteristic changes of pathologic myopia.
PURPOSE
To evaluate whether pigmented guinea pigs with spontaneous myopia present characteristic changes of pathologic myopia.
METHODS
The fundus images of guinea pigs (3 weeks old) were graded according to fundus tessellation (FT) degree. Biometric parameters, including refraction, vitreous chamber depth (VCD), and axial length (AL), were measured at ages 21 and 43 days. Some of these animals were divided into three groups: hyperopic without FT (H w/o FT), myopic without FT (M w/o FT), and myopic with FT (M w/ FT). The horizontal and vertical radii of curvature of posterior sclera (RP-H and RP-V, respectively) and the radii of curvature and arc lengths of superior sclera (RS and LS, respectively), inferior sclera (RI and LI, respectively), nasal sclera (RN and LN, respectively), and temporal sclera (RT and LT) were evaluated by Fuji.
RESULTS
The fundi were graded as type A or type B (both without FT), type C (mild FT), or type D (severe FT). The prevalence of FT was correlated with myopic refraction, longer VCD, and longer AL. Eyes of M w/FT animals had shorter RP-H and RP-V, longer RS and RT, and longer LS and LT than eyes of H w/o FT or M w/o FT animals. Refractions shifted toward hyperopia in eyes lacking FT, but not in eyes having FT. The changes in VCD were consistent with the changes in refraction. This relatively myopic shift in refraction and shortening of VCD were found only in myopic eyes with FT, but not in myopic eyes without FT.
CONCLUSIONS
Spontaneously myopic guinea pig eyes have a high prevalence of FT. Myopic eyes with FT presented characteristic signs of pathologic myopia.
Topics: Guinea Pigs; Animals; Myopia; Anterior Eye Segment; Posterior Eye Segment; Refraction, Ocular; Sclera; Hyperopia
PubMed: 37962527
DOI: 10.1167/iovs.64.14.19 -
IEEE Transactions on Medical Imaging Nov 2023We introduce a new concept of panoramic retinal (panretinal) optical coherence tomography (OCT) imaging system with a 140° field of view (FOV). To achieve this...
We introduce a new concept of panoramic retinal (panretinal) optical coherence tomography (OCT) imaging system with a 140° field of view (FOV). To achieve this unprecedented FOV, a contact imaging approach was used which enabled faster, more efficient, and quantitative retinal imaging with measurement of axial eye length. The utilization of the handheld panretinal OCT imaging system could allow earlier recognition of peripheral retinal disease and prevent permanent vision loss. In addition, adequate visualization of the peripheral retina has a great potential for better understanding disease mechanisms regarding the periphery. To the best of our knowledge, the panretinal OCT imaging system presented in this manuscript has the widest FOV among all the retina OCT imaging systems and offers significant values in both clinical ophthalmology and basic vision science.
Topics: Tomography, Optical Coherence; Retina
PubMed: 37216244
DOI: 10.1109/TMI.2023.3278269 -
Advanced Science (Weinheim,... Dec 2023Despite the significant progress in protein-based materials, creating a tunable protein-activated hydrogel lens remains an elusive goal. This study leverages the...
Despite the significant progress in protein-based materials, creating a tunable protein-activated hydrogel lens remains an elusive goal. This study leverages the synergistic relationship between protein structural dynamics and polymer hydrogel engineering to introduce a highly transparent protein-polymer actuator. By incorporating bovine serum albumin into polyethyleneglycol diacrylate hydrogels, the authors achieved enhanced light transmittance and conferred actuating capabilities to the hydrogel. Taking advantage of these features, a bilayer protein-driven hydrogel lens that dynamically modifies its focal length in response to pH changes, mimicking the adaptability of the human lens, is fabricated. The lens demonstrates durability and reproducibility, highlighting its potential for repetitive applications. This integration of protein-diverse biochemistry, folding nanomechanics, and polymer engineering opens up new avenues for harnessing the wide range of proteins to potentially propel various fields such as diagnostics, lab-on-chip, and deep-tissue bio-optics, advancing the understanding of incorporating biomaterials in the optical field.
Topics: Humans; Hydrogels; Reproducibility of Results; Biocompatible Materials; Lens, Crystalline; Polymers
PubMed: 37991134
DOI: 10.1002/advs.202306862 -
Investigative Ophthalmology & Visual... Mar 2024A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and... (Review)
Review
A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.
Topics: Humans; Adult; Aged; Macular Degeneration; Retina; Macula Lutea; Geographic Atrophy; Retinal Cone Photoreceptor Cells
PubMed: 38466281
DOI: 10.1167/iovs.65.3.4 -
Graefe's Archive For Clinical and... Aug 2023To demonstrate different topographic distributions of multiple-evanescent white dot syndrome (MEWDS) and secondary MEWDS disease and to describe possible associations.
PURPOSE
To demonstrate different topographic distributions of multiple-evanescent white dot syndrome (MEWDS) and secondary MEWDS disease and to describe possible associations.
METHODS
Clinical evaluation and multimodal retinal imaging in 27 subjects with MEWDS (29 discrete episodes of MEWDS). Ophthalmic assessment included best-corrected visual acuity testing and multimodal retinal imaging with OCT, blue-light autofluorescence, fluorescein and indocyanine green angiography, fundus photography, and widefield pseudocolor and autofluorescence fundus imaging.
RESULTS
The topographic distribution of MEWDS lesions was centered on or around the optic disc (n = 17, 59%), centered on the macula (n = 7, 24%), sectoral (n = 2, 7%), or was indeterminate (n = 3, 10%). The MEWDS episodes either occurred in the absence ('primary MEWDS'; n = 14, 48%) or presence of concurrent chorioretinal pathology ('secondary MEWDS'; n = 15, 52%). In patients with the latter, MEWDS lesions were often centered around a coexisting chorioretinal lesion. The majority of patients in both groups experienced resolution of their symptoms and retinal changes on multimodal imaging by 3 months.
CONCLUSIONS
Distinct distributions of MEWDS lesions were identified. MEWDS may occur in tandem with other chorioretinal pathology, which may impact the topography of MEWDS lesions.
Topics: Humans; Retinal Diseases; Tomography, Optical Coherence; Retina; White Dot Syndromes; Fluorescein Angiography
PubMed: 36988677
DOI: 10.1007/s00417-023-06032-1 -
Cells Nov 2023The corneal epithelium is the first anatomical barrier between the environment and the cornea; it is critical for proper light refraction onto the retina and prevents... (Review)
Review
The corneal epithelium is the first anatomical barrier between the environment and the cornea; it is critical for proper light refraction onto the retina and prevents pathogens (e.g., bacteria, viruses) from entering the immune-privileged eye. Trauma to the highly innervated corneal epithelium is extremely painful and if not resolved quickly or properly, can lead to infection and ultimately blindness. The healthy eye produces its own growth factors and is continuously bathed in tear fluid that contains these proteins and other nutrients to maintain the rapid turnover and homeostasis of the ocular surface. In this article, we review the roles of growth factors in corneal epithelial homeostasis and regeneration and some of the limitations to their use therapeutically.
Topics: Cornea; Epithelium, Corneal; Receptors, Growth Factor; Signal Transduction; Intercellular Signaling Peptides and Proteins; Homeostasis
PubMed: 38067157
DOI: 10.3390/cells12232730