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Investigative Ophthalmology & Visual... Jan 2017Autophagy and macropinocytosis are processes that are vital for cellular homeostasis, and help cells respond to stress and take up large amounts of material,... (Review)
Review
Autophagy and macropinocytosis are processes that are vital for cellular homeostasis, and help cells respond to stress and take up large amounts of material, respectively. The limbal and corneal epithelia have the machinery necessary to carry out both processes; however, autophagy and macropinocytosis are relatively understudied in these two epithelia. In this Perspectives, we describe the basic principles behind macropinocytosis and autophagy, discuss how these two processes are regulated in the limbal and corneal epithelia, consider how these two processes impact on the physiology of limbal and corneal epithelia, and elaborate on areas of future research in autophagy and macropinocytosis as related to the limbal/corneal epithelia.
Topics: Animals; Autophagy; Epithelium, Corneal; Humans; Limbus Corneae; Pinocytosis
PubMed: 28118670
DOI: 10.1167/iovs.16-21111 -
Experimental Eye Research May 2017Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of... (Review)
Review
Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or 'unconventional' route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans.
Topics: Animals; Aqueous Humor; Humans; Intraocular Pressure; Limbus Corneae; Models, Animal; Sclera; Secretory Pathway; Trabecular Meshwork; Uvea
PubMed: 26850315
DOI: 10.1016/j.exer.2016.01.017 -
The Ocular Surface Apr 2019The epithelial cell layer that covers the surface of the cornea provides a protective barrier while maintaining corneal transparency. The rapid and effective turnover of... (Review)
Review
The epithelial cell layer that covers the surface of the cornea provides a protective barrier while maintaining corneal transparency. The rapid and effective turnover of these epithelial cells depends, in part, on the limbal epithelial stem cells (LESCs) located in a specialized microenvironment known as the limbal niche. Many disorders affecting the regeneration of the corneal epithelium are related to deficiency and/or dysfunction of LESCs and the limbal niche. Current approaches for regenerating the corneal epithelium following significant injuries such as burns and inflammatory attacks are primarily aimed at repopulating the LESCs. This review summarizes and assesses the clinical feasibility and efficacy of current and emerging approaches for reconstruction of the limbal niche. In particular, the application of mesenchymal stem cells along with appropriate biological scaffolds appear to be promising strategies for long-term revitalization of the limbal niche.
Topics: Cell Count; Corneal Diseases; Epithelium, Corneal; Humans; Limbus Corneae; Stem Cell Niche; Stem Cell Transplantation
PubMed: 30633966
DOI: 10.1016/j.jtos.2019.01.002 -
JAMA Ophthalmology Jun 2020Limbal stem cell transplant (LSCT) can be categorized as direct autologous limbal transplant (AULT), direct allogenic limbal transplant (ALLT), cultivated autologous... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Limbal stem cell transplant (LSCT) can be categorized as direct autologous limbal transplant (AULT), direct allogenic limbal transplant (ALLT), cultivated autologous limbal stem cells transplant (cAULT), and cultivated allogenic limbal stem cells transplant (cALLT). To our knowledge, there is no study directly comparing the outcomes and complications of these procedures.
OBJECTIVE
To evaluate the outcomes of different LSCT procedures.
DATA SOURCE
We searched PubMed, EMBASE, Web of Science, and Cochrane without language filter for peer-reviewed articles about LSCT. The latest search was performed on June 30, 2019.
STUDY SELECTION
Clinical studies with the outcome of at least 20 eyes after LSCT were included. Animal studies and studies of other surgical interventions were excluded.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently abstracted the data from each study. Heterogeneity was evaluated with the I2 statistic, and a meta-analysis was performed using the random-effects model.
MAIN OUTCOMES AND MEASURES
Outcome measures included the improvement of ocular surface, visual acuity (VA), and adverse events of recipient eyes and donor eyes.
RESULTS
Forty studies (2202 eyes) with a mean (SD) follow-up of 31.3 (20.9) months met the inclusion criteria. The mean (SD) age of study participants was 38.4 (13.1) years, and men accounted for 74%. The number of eyes that underwent AULT, ALLT, cAULT, and cALLT were 505, 742, 771, and 184, respectively. Improvement of the ocular surface was achieved in 74.5% of all eyes, 85.7% of eyes after AULT (95% CI, 79.5%-90.3%), 84.7% after cAULT (95% CI, 77.2%-90.0%), 57.8% after ALLT (95% CI, 49.0%-66.1%), and 63.2% after cALLT (95% CI, 49.3%-75.2%). Autologous limbal transplantation resulted in a greater VA improvement rate (76%) than did the other 3 procedures (cAULT: 56.4%; ALLT: 52.3%; cALLT: 43.3%; all P < .001). The most common adverse events in all recipient eyes were recurrent/persistent epithelial erosion (10.5%; 95% CI, 7.2%-23.3%) and elevated intraocular pressure (intraocular pressure, 1.7%; 95% CI, 0.5%-7.8%). Patients who underwent ALLT had the highest rate of recurrent epithelial erosion (27.8%; 95% CI, 17.1%-41.9%) and intraocular pressure elevation (6.3%; 95% CI, 1.8%-19.4%).
CONCLUSIONS AND RELEVANCE
These findings suggest LSCT can improve or stabilize the corneal surface with a low rate of severe ocular complications and that autologous LSCT may have a higher success rate and fewer complications than allogenic LSCT.
Topics: Cells, Cultured; Corneal Diseases; Corneal Transplantation; Graft Survival; Humans; Limbus Corneae; Stem Cell Transplantation; Transplantation, Autologous; Visual Acuity
PubMed: 32324211
DOI: 10.1001/jamaophthalmol.2020.1120 -
The Indian Journal of Medical Research Jul 2021In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the... (Review)
Review
BACKGROUND & OBJECTIVES
In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the standardization of the management protocol for the same. In addition, there also exists diversity in the views about the clinical diagnosis, ancillary investigations and clinical parameters. The objective of the present study was to evaluate the reported outcomes of surgical interventions for the management of LSCD.
METHODS
A systematic review of published literature on limbal stem cell transplantation (LSCT) was performed using Ovid Medline, Embase and PubMed for a duration of 2009 to 2019. Original studies including prospective, retrospective case series and randomized controlled trials, articles in English language, articles with access to full text and studies with more than or at least 10 patients were included in this review. Data related to clinical and visual outcomes were evaluated, and pool estimates of different surgeries were calculated using random-effects model and individually using Pearson's Chi-square test.
RESULTS
A total of 1133 abstracts were evaluated. Finally, 17 studies were included for the analysis. Among these 17 studies, direct limbal lenticule transplantation was performed in five studies, of which autologous tissue from the fellow eye [conjunctival limbal autograft (CLAU)], allograft from a cadaver/live donor [keratolimbal allograft (KLAL)/conjunctival limbal allograft (CLAL)] and combination of CLAU plus KLAL were done in one, three and one studies, respectively. The ex vivo expanded cultivated limbal epithelial transplantation (CLET) was reported in six studies and simple limbal epithelial transplantation (SLET) in four studies. Two were comparative studies comparing CLET and CLAL (living-related CLAL) with cadaveric KLAL, respectively. Outcome analysis of the included studies showed significant heterogeneity. Calculated pool rate for various types of surgeries was calculated. The pool estimate for CLAL was 67.56 per cent [95% confidence interval (CI), 41.75-93.36; I=83.5%, P=0.002]. For KLAL, this value was 63.65 per cent (95% CI, 31.38-95.91; I=92.4%, P=0.000). Pool estimate for CLET was 78.90 per cent (95% CI, 70.51-87.28; I=73.6%, P=0.001). Corresponding values for SLET were 79.08 per cent (95% CI, 74.10-84.07; I=0.0%, P=0.619). CLAU and combination of CLAU plus KLAL were done in one study each; hence, statistical analysis could not be done. The functional outcome in terms of gain in visual acuity post-operatively was better in KLAL (P<0.005) and SLET group as compared to CLET group.
INTERPRETATION & CONCLUSIONS
The present analysis suggests that though the anatomical success rates were almost identical between SLET, CLET, CLAL, and KLAL procedures, the functional success rates were better following KLAL and SLET procedures as compared to CLET. Decision for LSCT for cases of ocular burns based on either clinical judgement of the surgeon or individual diagnosis remains a suitable option.
Topics: Corneal Diseases; Humans; Limbus Corneae; Prospective Studies; Randomized Controlled Trials as Topic; Retrospective Studies; Stem Cell Transplantation; Stem Cells; Transplantation, Autologous
PubMed: 34782530
DOI: 10.4103/ijmr.IJMR_1139_18 -
Medicine Jan 2021To introduce a limbus-centered continuous circular capsulorhexis (CCC) marking technique.Compared with traditional capsulotomy diameter mark technique, a self-designed... (Observational Study)
Observational Study
To introduce a limbus-centered continuous circular capsulorhexis (CCC) marking technique.Compared with traditional capsulotomy diameter mark technique, a self-designed limbus-centered capsulotomy mark (LCM) was used to perform the routine cataract surgery in this observational study. Ten eyes were included in each group. The area outer/inner 5.5-mm CCC ring, the furthest/nearest distance from the capsule margin to the intraocular lens (IOL) margin, the CCC total coverage IOL area were measured and compared between this 2 groups.No significant differences were found for all the comparison parameters between the 2 groups (all P > .05). However, the capsule total coverage area, area inner 5.5-mm ring was lower in the LCM group, which demonstrated advantage of LCM.The limbus-centered capsulotomy diameter mark, as an inexpensive and convenient method, helps to perform limbus-centered capsulorhexis with not only a 360° overlapping capsular edge but also well-centered IOL optics.
Topics: Capsulorhexis; China; Humans; Limbus Corneae; Phacoemulsification; Writing
PubMed: 33466181
DOI: 10.1097/MD.0000000000024109 -
Journal of Cellular and Molecular... Aug 2013The potential of stem cell (SC) therapies for eye diseases is well-recognized. However, the results remain only encouraging as little is known about the mechanisms...
The potential of stem cell (SC) therapies for eye diseases is well-recognized. However, the results remain only encouraging as little is known about the mechanisms responsible for eye renewal, regeneration and/or repair. Therefore, it is critical to gain knowledge about the specific tissue environment (niches) where the stem/progenitor cells reside in eye. A new type of interstitial cell-telocyte (TC) (www.telocytes.com) was recently identified by electron microscopy (EM). TCs have very long (tens of micrometres) and thin (below 200 nm) prolongations named telopodes (Tp) that form heterocellular networks in which SCs are embedded. We found TCs by EM and electron tomography in sclera, limbus and uvea of the mouse eye. Furthermore, EM showed that SCs were present in the anterior layer of the iris and limbus. Adhaerens and gap junctions were found to connect TCs within a network in uvea and sclera. Nanocontacts (electron-dense structures) were observed between TCs and other cells: SCs, melanocytes, nerve endings and macrophages. These intercellular 'feet' bridged the intercellular clefts (about 10 nm wide). Moreover, exosomes (extracellular vesicles with a diameter up to 100 nm) were delivered by TCs to other cells of the iris stroma. The ultrastructural nanocontacts of TCs with SCs and the TCs paracrine influence via exosomes in the epithelial and stromal SC niches suggest an important participation of TCs in eye regeneration.
Topics: Animals; Electron Microscope Tomography; Limbus Corneae; Mice; Mice, Inbred C57BL; Stem Cells; Uvea
PubMed: 23991685
DOI: 10.1111/jcmm.12111 -
PloS One 2018To present a novel non-parametric algorithm for detecting the position of the human eye limbus in three dimensions and a new dynamic method for measuring the full 360°...
PURPOSE
To present a novel non-parametric algorithm for detecting the position of the human eye limbus in three dimensions and a new dynamic method for measuring the full 360° visible iris boundary known as white-to-white distance along the eye horizontal line.
METHODS
The study included 88 participants aged 23 to 65 years (37.7±9.7), 47 females and 41 males. Clinical characteristics, height data and the apex coordinates and 1024×1280 pixel digital images of the eyes were taken by an Eye Surface Profiler and processed by custom-built MATLAB codes. A dynamic light intensity frequency based white-to-white detection process and a novel three-dimensional method for limbus detection is presented.
RESULTS
Evidence of significant differences (p<0.001) between nasal-temporal and superior-inferior white-to-white distances in both right and left eyes were found (nasal-temporal direction; 11.74±0.42 mm in right eyes and 11.82±0.47 mm in left eyes & superior-inferior direction; 11.52±0.45 mm in right eyes and 11.55±0.46 mm in left eyes). Average limbus nasal-temporal diameters were 13.64±0.55 mm for right eyes, and 13.74±0.40 mm for left eyes, however the superior-inferior diameters were 13.65±0.54 mm, 13.75±0.38 mm for right and left eyes, respectively. No significant difference in limbus contours has been observed either between the nasal-temporal direction (p = 0.91) and the superior-inferior direction (p = 0.83) or between the right (p = 0.18) and left eyes (p = 0.16). Evidence of tilt towards the nasal-temporal side in the three-dimensional shape of the limbus was found. The right eyes mean limbus contour tilt around the X-axis was -0.3±1.35° however, their mean limbus contour tilt around the Y-axis was 1.76±0.9°. Likewise, the left eyes mean limbus contour tilt around the X-axis was 0.77±1.25° and the mean limbus contour tilt around the Y-axis was -1.54±0.89°.
CONCLUSIONS
The white-to-white distance in the human eye is significantly larger in the nasal-temporal direction than in the superior-inferior direction. The human limbus diameter was found not to vary significantly in these directions. The 3D measures show that the limbus contour does not lay in one plane and tends to be higher on the nasal-inferior side of the eye.
Topics: Adult; Aged; Algorithms; Female; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Limbus Corneae; Male; Middle Aged; Young Adult
PubMed: 30475843
DOI: 10.1371/journal.pone.0207710 -
The Ocular Surface Jan 2018Limbal stem cells (LSCs) maintain the normal homeostasis and wound healing of corneal epithelium. Limbal stem cell deficiency (LSCD) is a pathologic condition that... (Review)
Review
Limbal stem cells (LSCs) maintain the normal homeostasis and wound healing of corneal epithelium. Limbal stem cell deficiency (LSCD) is a pathologic condition that results from the dysfunction and/or an insufficient quantity of LSCs. The diagnosis of LSCD has been made mainly based on medical history and clinical signs, which often are not specific to LSCD. Methods to stage the severity of LSCD have been lacking. With the application of newly developed ocular imaging modalities and molecular methods as diagnostic tools, standardized quantitative criteria for the staging of LSCD can be established. Because of these recent advancements, effective patient-specific therapy for different stages of LSCD may be feasible.
Topics: Corneal Diseases; Epithelium, Corneal; Humans; Limbus Corneae; Microscopy, Confocal; Stem Cells
PubMed: 29113917
DOI: 10.1016/j.jtos.2017.11.002 -
Frontiers in Bioscience (Scholar... Nov 2022Energy storage, transmission and dissipation are important considerations of normal mechanical homeostasis. In this paper we present a new technique termed vibrational...
BACKGROUND
Energy storage, transmission and dissipation are important considerations of normal mechanical homeostasis. In this paper we present a new technique termed vibrational optical coherence tomography (VOCT) to study the anterior anatomic structures of the pig eye to better understand how energy applied to the cornea is dissipated without delamination occurring.
METHODS
VOCT uses infrared light and an applied sinusoidal audible sound wave to image and measure the resonant frequency and modulus of individual macromolecular components of tissue non-invasively. We have measured the resonant frequencies and calculated the moduli of tissues in the anterior portion of the pig eye using VOCT.
RESULTS
While both pig and human eyes have similar resonant frequencies, they do differ in the peak amplitudes near the frequencies of 80, 120, 150 and 250 Hz. It is known that the stroma of pig cornea is much thicker than that of human corneas and these differences may explain the normalized peak height differences. The similarity of the resonant frequency peaks near 80, 120, 150 and 250 Hz of cornea, sclera and limbus suggest that the anatomically described layers in these tissues are connected into a single biomechanical unit that can store external mechanical energy and then transmit it for dissipation. Since the energy stored and dissipated is proportional to the modulus and the ability of the tissue to deform under stress, energy storage in these tissues is related to the stiffness.
CONCLUSIONS
It is concluded that stored energy is transmitted to the posterior segment of the eye for dissipation through the attachment with the sclera. This mechanism of energy dissipation may protect the cornea from changes in shape, curvature, and refractive power. However, ultimately, energy dissipation through thinning of the sclera may cause globe elongation observed in subjects with myopia and glaucoma.
Topics: Humans; Animals; Swine; Sclera; Elastic Modulus; Limbus Corneae; Cornea; Myopia
PubMed: 36575840
DOI: 10.31083/j.fbs1404030