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A Tenon's capsule/bulbar conjunctiva interface biomimetic to model fibrosis and local drug delivery.PloS One 2020Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but...
Glaucoma filtration surgery is one of the most effective methods for lowering intraocular pressure in glaucoma. The surgery efficiently reduces intra-ocular pressure but the most common cause of failure is scarring at the incision site. This occurs in the conjunctiva/Tenon's capsule layer overlying the scleral coat of the eye. Currently used antimetabolite treatments to prevent post-surgical scarring are non-selective and are associated with potentially blinding side effects. Developing new treatments to target scarring requires both a better understanding of wound healing and scarring in the conjunctiva, and new means of delivering anti-scarring drugs locally and sustainably. By combining plastic compression of collagen gels with a soft collagen-based layer, we have developed a physiologically relevant model of the sub-epithelial bulbar conjunctiva/Tenon's capsule interface, which allows a more holistic approach to the understanding of subconjunctival tissue behaviour and local drug delivery. The biomimetic tissue hosts both primary human conjunctival fibroblasts and an immune component in the form of macrophages, morphologically and structurally mimicking the mechanical proprieties and contraction kinetics of ex vivo porcine conjunctiva. We show that our model is suitable for the screening of drugs targeting scarring and/or inflammation, and amenable to the study of local drug delivery devices that can be inserted in between the two layers of the biomimetic. We propose that this multicellular-bilayer engineered tissue will be useful to study complex biological aspects of scarring and fibrosis, including the role of inflammation, with potentially significant implications for the management of scarring following glaucoma filtration surgery and other anterior ocular segment scarring conditions. Crucially, it uniquely allows the evaluation of new means of local drug delivery within a physiologically relevant tissue mimetic, mimicking intraoperative drug delivery in vivo.
Topics: Animals; Biomimetic Materials; Biomimetics; Cell Line; Cicatrix; Conjunctiva; Drug Delivery Systems; Drug Evaluation, Preclinical; Feasibility Studies; Fibroblasts; Fibrosis; Filtering Surgery; Glaucoma; Humans; Intraoperative Care; Monocytes; Postoperative Complications; Primary Cell Culture; Swine; Tenon Capsule; Wound Healing
PubMed: 33141875
DOI: 10.1371/journal.pone.0241569 -
Cells Mar 2022Severe ocular allergic diseases, such as atopic keratoconjunctivitis and vernal keratoconjunctivitis, cause severe allergic inflammation in the conjunctiva and corneal... (Review)
Review
Severe ocular allergic diseases, such as atopic keratoconjunctivitis and vernal keratoconjunctivitis, cause severe allergic inflammation in the conjunctiva and corneal epithelial damage, resulting in visual disturbances. The involvement of damage (danger)-associated molecular patterns (DAMPs/alarmins) in the pathogenesis of these diseases has been recognized. Alarmins released from damaged corneal epithelial cells or eosinophils play a critical role in the induction of corneal lesions, vicious loop of corneal injury, and exacerbation of conjunctival allergic inflammation. Alarmins in the conjunctiva also play an essential role in the development of both allergic inflammation, based on the acquired immune system, and type 2 inflammation by innate immune responses in the ocular surface. Therefore, alarmins may be a potentially important therapeutic target in severe refractory ocular allergic diseases.
Topics: Alarmins; Conjunctiva; Conjunctivitis, Allergic; Cornea; Humans; Inflammation
PubMed: 35326502
DOI: 10.3390/cells11061051 -
Ophthalmic Plastic and Reconstructive...The lateral tarsal strip (LTS) procedure is commonly used to correct eyelid malposition. When performing LTS, some surgeons elect to remove conjunctiva from the tarsal...
PURPOSE
The lateral tarsal strip (LTS) procedure is commonly used to correct eyelid malposition. When performing LTS, some surgeons elect to remove conjunctiva from the tarsal strip, while others do not. It has been hypothesized that without conjunctival stripping, the buried conjunctival tissue can cause complications such as inclusion cysts and granulomas. However, there is limited data comparing LTS cases with and without conjunctiva removal. The authors sought to evaluate whether conjunctival stripping had any impact on complication rates with LTS.
METHODS
LTS operations for ectropion correction were retrospectively reviewed and were separated into 2 cohorts, Con (conjunctiva not removed) or Coff (conjunctival removed). Charts were reviewed for outcomes and complications including inclusion cyst formation, granuloma formation, wound dehiscence, infection, and focal rim tenderness.
RESULTS
The complication rate was 10% versus 8% for Con versus Coff respectively ( p = 0.54). The common complications of LTS surgery were granuloma (4%), wound dehiscence (3%), focal rim tenderness (3%), and infection requiring antibiotics (<1%). There was no significant difference in these complications between the Con and Coff cohorts.
CONCLUSIONS
Complications in both groups were minimal, similar to prior studies, and there was no difference between the 2 cohorts. While it has been suggested that buried conjunctiva may result in increased complication rates, the author's findings suggest that removing the tarsal conjunctiva is a superfluous step in the LTS surgery and does not affect complication rates.
Topics: Blepharoplasty; Conjunctiva; Ectropion; Eyelids; Humans; Postoperative Complications; Retrospective Studies; Suture Techniques
PubMed: 35323138
DOI: 10.1097/IOP.0000000000002159 -
The Ocular Surface Apr 2020The conjunctiva is a goblet cell rich mucosal tissue. Goblet cells are supported by tear growth factors and IL-13 produced by resident immune cells. Goblet cell... (Review)
Review
The conjunctiva is a goblet cell rich mucosal tissue. Goblet cells are supported by tear growth factors and IL-13 produced by resident immune cells. Goblet cell secretions are essential for maintaining tear stability and ocular surface homeostasis. In addition to producing tear stabilizing mucins, they also produce cytokines and retinoic acid that condition monocyte-derived phagocytic cells in the conjunctiva. Aqueous tear deficiency from lacrimal gland disease and systemic inflammatory conditions results in goblet cell loss that amplifies dry eye severity. Reduced goblet cell density is correlated with more severe conjunctival disease, increased IFN-γ expression and antigen presenting cell maturation. Sterile Alpha Motif (SAM) pointed domain epithelial specific transcription factor (Spdef) gene deficient mice that lack goblet cells have increased infiltration of monocytes and dendritic cells with greater IL-12 expression in the conjunctiva. Similar findings were observed in the conjunctiva of aged mice. Reduced retinoic acid receptor (RXRα) signaling also increases conjunctival monocyte infiltration, IFN-γ expression and goblet cell loss. Evidence suggests that dry eye therapies that suppress IFN-γ expression preserve conjunctival goblet cell number and function and should be considered in aqueous deficiency.
Topics: Animals; Cell Communication; Conjunctiva; Dry Eye Syndromes; Goblet Cells; Mice, Knockout; Tears
PubMed: 31953222
DOI: 10.1016/j.jtos.2019.12.006 -
Indian Journal of Ophthalmology Jul 2023Pigmented lesions in the conjunctiva can be baffling to both the patients and the treating ophthalmologist because of their varied range of presentation and overlapping...
BACKGROUND
Pigmented lesions in the conjunctiva can be baffling to both the patients and the treating ophthalmologist because of their varied range of presentation and overlapping clinical features. The lesions range from incidental pigment deposition such as mascara and complexion-associated melanosis to malignant melanoma which poses a risk to life. Similarly, the management ranges from observation at regular intervals to aggressive surgery like exenteration.
PURPOSE
We wanted to present a crisp and precise video of the good, bad, and ugly pigmented lesions of the conjunctiva, highlighting their specific clinical features important for the diagnosis and their management.
SYNOPSIS
This video describes the myriad of pigmented conjunctival lesions, their diagnostic characteristics, and management based on oncological principles.
LINK
https://drive.google.com/file/d/1BYJ51rQtqjwM6e73BwrrLqdC1EoXA8Eu/view?usp=sharing.
HIGHLIGHTS
: Pigmented lesions can have variable presentation and close mimics, therefore, it is important to differentiate and identify the lesions accurately. This video highlights different pigmented lesions and their individual characteristic features. Video link https://youtu.be/m9tt7dx9SWc.
Topics: Conjunctiva; Conjunctival Neoplasms; Melanosis; Nevus, Pigmented; Skin Neoplasms; Humans
PubMed: 37417160
DOI: 10.4103/IJO.IJO_1367_23 -
Stem Cells Translational Medicine Jul 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID-19) pandemic.... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first emerged in December 2019 and spread quickly causing the coronavirus disease 2019 (COVID-19) pandemic. Recent single cell RNA-Seq analyses have shown the presence of SARS-CoV-2 entry factors in the human corneal, limbal, and conjunctival superficial epithelium, leading to suggestions that the human ocular surface may serve as an additional entry gateway and infection hub for SARS-CoV-2. In this article, we review the ocular clinical presentations of COVID-19 and the features of the ocular surface that may underline the overall low ocular SARS-CoV-2 infection. We critically evaluate the studies performed in nonhuman primates, ex vivo organ culture ocular models, stem cell derived eye organoids and the differences in infection efficiency observed in different parts of human ocular surface epithelium. Finally, we highlight the additional work that needs to be carried out to understand the immune response of the ocular surface to SARS-CoV-2 infection, which can be translated into prophylactic treatments that may be applied to other organ systems.
Topics: COVID-19; Conjunctiva; Cornea; Eye Diseases; Humans; SARS-CoV-2; Virus Replication
PubMed: 33710758
DOI: 10.1002/sctm.20-0543 -
The Ocular Surface Jul 2021The translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation of the conjunctival microvasculature consisting of... (Review)
Review
The translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation of the conjunctival microvasculature consisting of extensive branching of superficial and deep arterial systems and corresponding drainage pathways, and the translucent appearance of the conjunctiva allows for immediate visualization of changes in the circulation. Conjunctival hyperemia is caused by a pathological vasodilatory response of the microvasculature in response to inflammation due to a myriad of infectious and non-infectious etiologies. It is one of the most common contributors of ocular complaints that prompts visits to medical centers. Our understanding of these neurogenic and immune-mediated pathways has progressed over time and has played a critical role in developing targeted novel therapies. Due to a multitude of underlying etiologies, patients must be accurately diagnosed for efficacious management of conjunctival hyperemia. The diagnostic techniques used for the grading of conjunctival hyperemia have also evolved from descriptive and subjective grading scales to more reliable computer-based objective grading scales.
Topics: Conjunctiva; Conjunctivitis; Humans; Hyperemia; Inflammation
PubMed: 34010701
DOI: 10.1016/j.jtos.2021.05.003 -
Ophthalmic Surgery, Lasers & Imaging... May 2022To describe conjunctiva and Tenon's capsule handling during the Port Delivery System with ranibizumab (PDS) implant insertion procedure including up-front assessments,...
OBJECTIVES
To describe conjunctiva and Tenon's capsule handling during the Port Delivery System with ranibizumab (PDS) implant insertion procedure including up-front assessments, planning, and instrumentation, with emphasis placed on the peritomy, scleral dissection, and closure steps.
METHODS
Surgical pearls based on experience accumulated in the PDS clinical trial program in patients with retinal diseases.
RESULTS
Preoperative preparation, specific instruments, and meticulous techniques are key to optimizing surgical outcomes. Before surgery, assessment of factors that affect conjunctival integrity and an in-office conjunctiva examination are conducted. Gentle, purposeful conjunctiva and Tenon's capsule handling with nontoothed forceps and suturing with a BV needle are recommended to prevent tissue damage. The peritomy is 6 mm by 6 mm, centered around the planned implant location in the superotemporal quadrant. A complete sub-Tenon's capsule dissection is achieved using a wide, robust lateral and posterior dissection technique to free tissue from the sclera and minimize tension. The globe is stabilized during scleral cutdown by grasping the sclera with fine-toothed forceps away from the incision edge to prevent tissue delamination. When closing the peritomy, both the conjunctiva and Tenon's capsule are completely captured and sutured with scleral anchoring at the apex of the peritomy to help prevent conjunctival retraction and erosion. Mitigation and detection of adverse events is critical to successful surgical outcomes.
CONCLUSIONS
The PDS implant insertion procedure is straightforward, but it requires planned preoperative preparation, specific instruments, and meticulous techniques. The surgical pearls described here offer insights for optimizing outcomes. .
Topics: Conjunctiva; Humans; Ranibizumab; Sclera; Surgical Flaps; Tenon Capsule
PubMed: 35575739
DOI: 10.3928/23258160-20220415-03 -
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 -
International Journal of Molecular... Mar 2022Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics... (Review)
Review
Sex hormones are molecules produced by the gonads and to a small extent by the adrenal gland, which not only determine the primary and secondary sexual characteristics of an individual, differentiating man from woman, but also participate in the functioning of the various systems of the body. The evidence that many eye diseases differ in terms of prevalence between men and women has allowed us, in recent years, to carry out several studies that have investigated the association between sex hormones and the pathophysiology of eye tissues. Specific receptors for sex hormones have been found on the lacrimal and meibomian glands, conjunctiva, cornea, lens, retina, and choroid. This work summarizes the current knowledge on the role that sex hormones play in the pathogenesis of the most common ocular disorders and indicates our clinical experience in these situations. The aim is to stimulate an interdisciplinary approach between endocrinology, neurology, molecular biology, and ophthalmology to improve the management of these diseases and to lay the foundations for new therapeutic strategies.
Topics: Conjunctiva; Cornea; Eye Diseases; Female; Gonadal Steroid Hormones; Humans; Lacrimal Apparatus; Male; Meibomian Glands
PubMed: 35328690
DOI: 10.3390/ijms23063269