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Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: closed (25 September 2021) | Viewed by 42420

Special Issue Editor

Dr. Antonio Di Zazzo

E-Mail Website
Guest Editor
Ophthalmology Complex Unit, Campus Bio-Medico University Hospital, Rome, Italy
Interests: cornea; corneal transplantation; dry eye disease; allergy; corneal angiogenesis; immunology; refractive surgery; stem cell transplantation; keratoprosthesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The ocular surface is a complex, morpho-functional unit in which multiple anatomical and cellular components (cornea, conjunctivae, lacrimal glands, Meibomian glands, tear film, immune cells and nervous fibers) cooperate to preserve homeostasis. This equilibrium promotes the repair of the ocular surface following daily repetitive insults. Self-limiting innate immune mechanisms maintain and restore homeostasis and permit tissues to adapt to injuries and restore their normal functions. However, if dysregulated, it may trigger overt inflammation, resulting in the clinical signs observed in several ocular chronic disorders.

Such dysfunction may possibly be due to neurogenic, immune, metabolic and hormonal alterations which dysregulate the normal healthy equilibrium. In such patients, the dysregulated inflammatory response is not self-limiting but persistent, leading to a critical shift in homeostatic baseline towards inflammation with changes in immune-responsiveness and vulnerability to illness, underlining the loss of homeostatic ability of ocular surface, as in other conditions, such as ageing.

The aim of this Special Issue is to investigate clinical and molecular inflammatory changes at the ocular surface in several ocular surface diseases in which such homeostatic mechanisms are dysregulated, showing persistent-chronic, subliclinical or excessive inflammatory response despite the insult.

Dr. Antonio Di Zazzo
Guest Editor

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Keywords

  • dry eye disease
  • ocular surface diseases
  • ageing
  • allergy
  • chronic cicatrizing conjunctivitis
  • ocular surface diabetic disease
  • polycystic ovary syndrome

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Published Papers (10 papers)

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Editorial

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3 pages, 184 KiB  
Editorial
Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit
by Antonio Di Zazzo
J. Clin. Med. 2022, 11(16), 4685; https://doi.org/10.3390/jcm11164685 - 11 Aug 2022
Cited by 1 | Viewed by 1271
Abstract
The ocular surface is a morpho-functional system in which multiple components such as cornea, conjunctiva, principal and accessory lacrimal glands, tear film, endocrine, immune, and nervous system cooperate to preserve local health [...] Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)

Research

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6 pages, 1182 KiB  
Article
Ocular Surface Failure in Urban Syndrome
by Marco Antonini, Daniele Gaudenzi, Sara Spelta, Giancarlo Sborgia, Maria Poddi, Alessandra Micera, Roberto Sgrulletta, Marco Coassin and Antonio Di Zazzo
J. Clin. Med. 2021, 10(14), 3048; https://doi.org/10.3390/jcm10143048 - 9 Jul 2021
Cited by 12 | Viewed by 2221
Abstract
Background: Nowadays, the continuous increase in air pollution has significantly changed air quality, leading to the onset of the so-called urban syndrome (US), an allergic-like conjunctivitis triggered by pollutants. These patients are characterized by persistent dysregulation of ocular surface para-inflammation, causing chronic low-grade [...] Read more.
Background: Nowadays, the continuous increase in air pollution has significantly changed air quality, leading to the onset of the so-called urban syndrome (US), an allergic-like conjunctivitis triggered by pollutants. These patients are characterized by persistent dysregulation of ocular surface para-inflammation, causing chronic low-grade inflammation and ocular discomfort, with significant consequences for occupational health and job productivity prospects. This study aims to investigate the effects of topical glycerophosphoinositol (GPI) eye drops on the signs and symptoms of US. Methods: A multicenter prospective open interventional study was performed. Patients affected by US, enrolled from occupational medicine clinics, were treated with eye drops containing 0.001% GPI in 0.2% HA vehicle three times a day. Ocular surface disease index (OSDI), tear break-up time (T-BUT), Schirmer test, Oxford score, hyperemia and ocular surface symptoms were recorded at patient enrolment (T0), after 1 week (T1) and after 1 month (T2) of treatment. Results: A total of 113 consecutive patients (226 eyes) were included. OSDI score displayed a significant improvement after one week (T0: 39.9 ± 19, T1: 20.8 ± 17.9, T2: 18.4 ± 15.6, p < 0.0001); T-BUT (T0: 5.2 ± 2, T1: 7.7 ± 2.2, T2: 9.7 ± 1.8, p < 0.0001) and Schirmer Test (T0: 6.6 ± 2.4, T1: 9.7 ± 2.7, T2: 12.6 ± 2.6, p < 0.0001) progressively improved from T0 to T2. Conclusions: trice-daily topic instillation of 0.001% GPI in 0.02% HA vehicle resulted an effective and well tolerated treatment in US patients. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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11 pages, 1832 KiB  
Article
Lycium barbarum Polysaccharide Suppresses Expression of Fibrotic Proteins in Primary Human Corneal Fibroblasts
by Sum Sum Kwok, Francisca Siu-Yin Wong, Kendrick Co Shih, Yau-Kei Chan, Yashan Bu, Tommy Chung-Yan Chan, Alex Lap-Ki Ng, Amy Cheuk-Yin Lo, Louis Tong, Gary Hin-Fai Yam and Vishal Jhanji
J. Clin. Med. 2020, 9(11), 3572; https://doi.org/10.3390/jcm9113572 - 6 Nov 2020
Cited by 10 | Viewed by 2899
Abstract
(1) Objective: To study the anti-fibrotic effects of Lycium barbarum polysaccharides (LBP) on corneal stromal fibroblasts and assess LBP’s effect on cell viability. (2) Methods: Primary human corneal keratocytes of passage 3 to 6 were used for all experiments. Cells are pretreated with [...] Read more.
(1) Objective: To study the anti-fibrotic effects of Lycium barbarum polysaccharides (LBP) on corneal stromal fibroblasts and assess LBP’s effect on cell viability. (2) Methods: Primary human corneal keratocytes of passage 3 to 6 were used for all experiments. Cells are pretreated with LBP solution for 24 h and then transforming growth factor beta 1 (TGFβ1) for 48 h and collected for experiments. Fibrotic protein analysis was performed using immunofluorescence and Western blot. The effect of LBP on cell viability was assessed using the MTS assay. (3) Results: LBP significantly reduced the expression of fibrotic proteins, including α-SMA and extracellular matrix proteins (collagen type I and III). LBP significantly decreased the viability of myofibroblasts but not the fibroblasts. Conclusions: In this study, LBP was effective in the prevention of fibrosis gene expression. Further studies to assess the underlying mechanism and pharmacological properties will facilitate the formation of a topical LBP solution for in vivo studies. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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12 pages, 5090 KiB  
Article
Comparison of the Meibomian Gland Openings by Optical Coherence Tomography in Obstructive Meibomian Gland Dysfunction and Normal Patients
by Xinhan Cui, Qingfan Wu, Zimeng Zhai, Yujing Yang, Anji Wei, Jianjiang Xu and Jiaxu Hong
J. Clin. Med. 2020, 9(10), 3181; https://doi.org/10.3390/jcm9103181 - 30 Sep 2020
Cited by 8 | Viewed by 3438
Abstract
Purpose: The aim of this study was to use swept-source anterior segment optical coherence tomography (OCT) to explore imaging the meibomian gland openings and to identify their in vivo characteristics in patients with obstructive meibomian gland dysfunction (MGD) and healthy participants. Methods: We [...] Read more.
Purpose: The aim of this study was to use swept-source anterior segment optical coherence tomography (OCT) to explore imaging the meibomian gland openings and to identify their in vivo characteristics in patients with obstructive meibomian gland dysfunction (MGD) and healthy participants. Methods: We enrolled 49 patients with MGD and 54 health controls in this case-control study. Each participant underwent slit-lamp examination, meibography, and OCT scanning. Sixteen patients with MGD underwent a repeat OCT examination after eyelid massage. The outcome measures included determinations of meibomian gland openings (orifices and terminal ducts) from OCT images and comparisons of the meibomian openings between patients with MGD and normal controls before and after meibomian gland massage. Results: Using the same OCT scanning model, the number of visible orifices of the meibomian glands was similar between eyes with MGD and normal eyes (9.2 ± 2.3 vs. 9.7 ± 2.4). The mean diameter of the terminal ducts in patients with MGD was larger (120.22 ± 27.92 µm vs. 100.96 ± 20.30 µm) than in the normal controls, and had a larger coefficient of variation. Significant differences were observed in the mean diameter of the terminal ducts of patients with MGD before and after meibum gland massage (133.73 ± 27.81 μm vs. 102.26 ± 24.30 μm, p < 0.001). Conclusions: Patients with MGD have more diversified orifices and larger meibomian gland terminal duct diameters than normal subjects. In addition, meibomian gland terminal duct diameters seem to decrease in patients with MGD after meibum gland massage. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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Review

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12 pages, 596 KiB  
Review
A Review of the Impact of Alterations in Gut Microbiome on the Immunopathogenesis of Ocular Diseases
by Yashan Bu, Yau-Kei Chan, Ho-Lam Wong, Stephanie Hiu-Ling Poon, Amy Cheuk-Yin Lo, Kendrick Co Shih and Louis Tong
J. Clin. Med. 2021, 10(20), 4694; https://doi.org/10.3390/jcm10204694 - 13 Oct 2021
Cited by 15 | Viewed by 3689
Abstract
Recent studies have highlighted the association between ocular diseases and microbiota profiles of the host intestinal tract and oral cavity. There is mounting evidence supporting the existence of a ‘gut–eye axis’, whereby changes in gut microbiome alter host immunity, with consequential implications for [...] Read more.
Recent studies have highlighted the association between ocular diseases and microbiota profiles of the host intestinal tract and oral cavity. There is mounting evidence supporting the existence of a ‘gut–eye axis’, whereby changes in gut microbiome alter host immunity, with consequential implications for ocular health and disease. In this review, we examined recent published findings on the association between gut microbiome and ocular morbidity, based on 25 original articles published between 2011 to 2020. The review included both clinical and in vivo animal studies, with particular focus on the influence of the microbiome on host immunity and metabolism. Significant associations between altered intestinal microbiome and specific ocular diseases and pathological processes, including Behçet’s syndrome, autoimmune uveitis, age-related macular degeneration, choroidal neovascularization, bacterial keratitis, and Sjögren-like lacrimal keratoconjunctivitis have been demonstrated. Furthermore, alterations in the gut microbiome resulted in quantifiable changes in the host immune response, suggesting immunopathogenesis as the basis for the link between intestinal dysbiosis and ocular disease. We also examined and compared different techniques used in the identification and quantification of gut microorganisms. With our enhanced understanding of the potential role of gut commensals in ophthalmic disease, the stage is set for further studies on the underlying mechanisms linking the gut microbiome, the host immune response, and the pathogenesis of ophthalmic disease. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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20 pages, 2070 KiB  
Review
Role of Immune Cell Diversity and Heterogeneity in Corneal Graft Survival: A Systematic Review and Meta-Analysis
by Jun Zhu, Takenori Inomata, Antonio Di Zazzo, Koji Kitazawa, Yuichi Okumura, Marco Coassin, Pier Luigi Surico, Kenta Fujio, Ai Yanagawa, Maria Miura, Yasutsugu Akasaki, Keiichi Fujimoto, Ken Nagino, Akie Midorikawa-Inomata, Kunihiko Hirosawa, Mizu Kuwahara, Tianxiang Huang, Hurramhon Shokirova, Atsuko Eguchi and Akira Murakami
J. Clin. Med. 2021, 10(20), 4667; https://doi.org/10.3390/jcm10204667 - 12 Oct 2021
Cited by 16 | Viewed by 2985
Abstract
Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction [...] Read more.
Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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27 pages, 1830 KiB  
Review
The Role of Neuropeptides in Pathogenesis of Dry Eye
by Daniel Duck-Jin Hwang, Seok-Jae Lee, Jeong-Hun Kim and Sang-Mok Lee
J. Clin. Med. 2021, 10(18), 4248; https://doi.org/10.3390/jcm10184248 - 19 Sep 2021
Cited by 13 | Viewed by 4976
Abstract
Neuropeptides are known as important mediators between the nervous and immune systems. Recently, the role of the corneal nerve in the pathogenesis of various ocular surface diseases, including dry eye disease, has been highlighted. Neuropeptides are thought to be important factors in the [...] Read more.
Neuropeptides are known as important mediators between the nervous and immune systems. Recently, the role of the corneal nerve in the pathogenesis of various ocular surface diseases, including dry eye disease, has been highlighted. Neuropeptides are thought to be important factors in the pathogenesis of dry eye disease, as suggested by the well-known role between the nervous and immune systems, and several recently published studies have elucidated the previously unknown pathogenic mechanisms involved in the role of the neuropeptides secreted from the corneal nerves in dry eye disease. Here, we reviewed the emerging concept of neurogenic inflammation as one of the pathogenic mechanisms of dry eye disease, the recent results of related studies, and the direction of future research. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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15 pages, 1233 KiB  
Review
Sex Hormones Related Ocular Dryness in Breast Cancer Women
by Antonella Grasso, Antonio Di Zazzo, Giuseppe Giannaccare, Jaemyoung Sung, Takenori Inomata, Kendrick Co Shih, Alessandra Micera, Daniele Gaudenzi, Sara Spelta, Maria Angela Romeo, Paolo Orsaria, Marco Coassin and Vittorio Altomare
J. Clin. Med. 2021, 10(12), 2620; https://doi.org/10.3390/jcm10122620 - 14 Jun 2021
Cited by 15 | Viewed by 3983
Abstract
Background: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hormones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical manifestation as dry [...] Read more.
Background: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hormones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical manifestation as dry eye disease. This local dryness is part of the breast cancer iatrogenic dryness, which affects overall mucosal tissue in the fragile population of those with breast cancer. Methods: A literature review regarding the role of sex hormone changes and systemic hormonal replacement treatments (SHRT) in DES available on PubMed and Web of Science was made without any restriction of language. Results: Androgens exert their role on the ocular surface supporting meibomian gland function and exerting a pro-sebaceous effect. Estrogen seems to show a pro/inflammatory role on the ocular surface, while SHRT effects on dry eye are still not well defined, determining apparently contradictory consequences on the ocular surface homeostasis. The role of sex hormones on dry eye pathogenesis is most likely the result of a strict crosstalk between the protective androgens effects and the androgen-modulating effects of estrogens on the meibomian glands. Conclusions: Patients with a pathological or iatrogenic hormonal imbalance, such as in the case of breast cancer, should be assessed for dry eye disease, as well as systemic dryness, in order to restore their social and personal quality of life. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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10 pages, 10072 KiB  
Review
Challenges in Acanthamoeba Keratitis: A Review
by Giuseppe Varacalli, Antonio Di Zazzo, Tommaso Mori, Thomas H. Dohlman, Sara Spelta, Marco Coassin and Stefano Bonini
J. Clin. Med. 2021, 10(5), 942; https://doi.org/10.3390/jcm10050942 - 1 Mar 2021
Cited by 47 | Viewed by 11650
Abstract
To review challenges in the diagnosis and management of Acanthamoeba keratitis (AK), along with prognostic factors, in order to help ophthalmologists avoid misdiagnosis, protracted treatment periods, and long-term negative sequelae, with an overarching goal of improving patient outcomes and quality of life, we [...] Read more.
To review challenges in the diagnosis and management of Acanthamoeba keratitis (AK), along with prognostic factors, in order to help ophthalmologists avoid misdiagnosis, protracted treatment periods, and long-term negative sequelae, with an overarching goal of improving patient outcomes and quality of life, we examined AK studies published between January 1998 and December 2019. All manuscripts describing clinical manifestations, diagnosis, treatment, prognosis, and challenges in short- and long-term management were included. The diagnosis of AK is often challenging. An increased time between symptom onset and the initiation of appropriate therapy is associated with poorer visual outcomes. The timely initiation of standardized antiamoebic therapies improves visual outcomes, decreases the duration of treatment, and reduces the chances of needing surgical intervention. In clinical practice, AK diagnosis is often missed or delayed, leading to poorer final visual outcomes and a negative impact on patient morbidity and quality of life. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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12 pages, 857 KiB  
Review
CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization and Wound Healing
by Francesco Aiello, Gabriele Gallo Afflitto, Ji-Peng Olivia Li, Alessio Martucci, Massimo Cesareo and Carlo Nucci
J. Clin. Med. 2020, 9(12), 4036; https://doi.org/10.3390/jcm9124036 - 14 Dec 2020
Cited by 16 | Viewed by 3575
Abstract
The endocannabinoid system (ECS) is a complex regulatory system, highly conserved among vertebrates. It has been widely described in nearly all human tissues. In the conjunctiva and cornea, the ECS is believed to play a pivotal role in the modulation of the local [...] Read more.
The endocannabinoid system (ECS) is a complex regulatory system, highly conserved among vertebrates. It has been widely described in nearly all human tissues. In the conjunctiva and cornea, the ECS is believed to play a pivotal role in the modulation of the local inflammatory state as well as in the regulation of tissue repair and fibrosis, neo-angiogenesis and pain perception. This review aims to summarize all the available data on ECS expression and its function in ocular surface structures to provide a specific insight concerning its modulation in dry eye disease, and to propose directions for future research. Full article
(This article belongs to the Special Issue Pathogenesis of the Homeostatic Failure of Ocular Surface as Morpho-Functional Unit)
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