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Molecular and Immunological Approaches in Ophthalmology: Inflammatory Disorders
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Molecular and Immunological Approaches in Ophthalmology: Inflammatory Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (10 December 2022) | Viewed by 11128

Special Issue Editor

Dr. Lourdes A. Fortepiani

E-Mail Website
Guest Editor
Rosenberg School of Optometry, University of the Incarnate Word, San Antonio, TX, USA
Interests: hypertension; diabetes; sex differences; oxidative stress; inflammation; kidney; ocular

Special Issue Information

Dear Colleagues,

Ocular inflammatory disorders affect primarily the uveal tract but also include other locations, such as the ocular surface, conjunctiva, cornea, sclera, retina, retinal vessels, and the optic nerve. Accurate diagnosis is key in the management of ocular inflammation from benign, self-limited conditions to sight threatening disorders. In the past few years, imaging diagnostic techniques have advanced significantly, including optical coherence tomography (OCT) but do not distinguish between different etiologic or pathogenetic factors which makes the therapeutic approach challenging, impacting the patient’s quality of life. Complementing imaging tools, new molecular techniques have contributed to a better understanding of the pathogenesis of some noninfectious ocular disorders but also provided a more sensitive and specific diagnosis of infectious causes. Further understanding of these molecular pathways has allowed the development of novel immunosuppressive therapies as an alternative to the classic corticosteroid treatment as well as preserving the immune privilege in the eye.

For this Special Issue, we would like to invite papers that discuss the use of molecular and immunological approaches for diagnosis or treatment of ocular inflammatory disorders. Suggested areas are classic uveitis disorders, ocular manifestations of systemic inflammatory disorders, post-surgical ocular inflammatory presentations, as well as those derived from non-classical inflammatory disorders (such as age-related macular degeneration and macular edema secondary to diabetic retinopathy). Although pure clinical research does not meet our journal's aim and scope, clinical data added with molecular mechanical studies will be warmly welcomed.

Dr. Lourdes A. Fortepiani
Guest Editor

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Keywords

  • diagnosis
  • uveitis
  • keratitis
  • ocular inflammation
  • hypersensitivity
  • cell surface molecules
  • antibodies
  • cytokines
  • autoimmunity
  • therapeutic

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Published Papers (4 papers)

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Research

11 pages, 3959 KiB  
Article
PLDLA/TPU Matrix Enriched with Cyclosporine A as a Therapeutic Platform for Immune-Mediated Keratitis (IMMK) in Horses
by Martyna Padjasek, Anna Cisło-Sankowska, Anna Lis-Bartos, Badr Qasem and Krzysztof Marycz
Int. J. Mol. Sci. 2023, 24(6), 5735; https://doi.org/10.3390/ijms24065735 - 17 Mar 2023
Cited by 2 | Viewed by 2656
Abstract
The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as [...] Read more.
The purpose of this study was to describe the use of PLDLA/TPU matrix enriched with cyclosporine A (CsA) as a therapeutic platform in horses with immune-mediated keratitis (IMMK) with an in vitro evaluation CsA release and degradation of the blend as well as determination of the safety and efficacy of that platform used in the animal model. The kinetics of the CsA release from matrices constructed of thermoplastic polyurethane (TPU) polymer and a copolymer of L-lactide with DL-lactide (PLDLA) (80:20) in the TPU (10%) and a PLDL (90%) polymer blend were studied. Moreover, we used the STF (Simulated Tear Fluid) at 37 °C as a biological environment to assess the CsA release and its degradation. Additionally, the platform described above was injected subconjunctival in the dorsolateral quadrant of the globe after standing sedation of horses with diagnosed superficial and mid-stromal IMMK. The obtained results indicated that the CsA release rate in the fifth week of the study increased significantly by the value of 0.3% compared to previous weeks. In all of the cases, the TPU/PLA doped with 12 mg of the CsA platform effectively reduced the clinical symptoms of keratitis, leading to the complete remission of the corneal opacity and infiltration four weeks post-injection. The results from this study showed that the PLDLA/TPU matrix enriched with the CsA platform was well tolerated by the equine model and effective in treating superficial and mid-stromal IMMK. Full article
(This article belongs to the Special Issue Molecular and Immunological Approaches in Ophthalmology: Inflammatory Disorders)
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10 pages, 2519 KiB  
Article
Inflammation Confers Healing Advantage to Corneal Epithelium Following Subsequent Injury
by Jin Suk Ryu, So Yeon Kim, Mee Kum Kim and Joo Youn Oh
Int. J. Mol. Sci. 2023, 24(4), 3329; https://doi.org/10.3390/ijms24043329 - 7 Feb 2023
Cited by 4 | Viewed by 2693
Abstract
Recent evidence shows that epithelial stem/progenitor cells in barrier tissues such as the skin, airways and intestines retain a memory of previous injuries, which enables tissues to accelerate barrier restoration after subsequent injuries. The corneal epithelium, the outermost layer of the cornea, is [...] Read more.
Recent evidence shows that epithelial stem/progenitor cells in barrier tissues such as the skin, airways and intestines retain a memory of previous injuries, which enables tissues to accelerate barrier restoration after subsequent injuries. The corneal epithelium, the outermost layer of the cornea, is the frontline barrier for the eye and is maintained by epithelial stem/progenitor cells in the limbus. Herein, we provide evidence that inflammatory memory also exists in the cornea. In mice, eyes that had been exposed to corneal epithelial injury exhibited faster re-epithelialization of the cornea and lower levels of inflammatory cytokines following subsequent injury (either the same or a different type of injury) relative to naïve eyes without previous injury. In ocular Sjögren’s syndrome patients, corneal punctate epithelial erosions were significantly reduced after experiencing infectious injury compared with before. These results demonstrate that previous exposure of the corneal epithelium to inflammatory stimuli enhances corneal wound healing in response to a secondary assault, a phenomenon which points to the presence of nonspecific inflammatory memory in the cornea. Full article
(This article belongs to the Special Issue Molecular and Immunological Approaches in Ophthalmology: Inflammatory Disorders)
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12 pages, 5764 KiB  
Article
Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro
by Anne L. C. Hoffmann, Stefanie M. Hauck, Cornelia A. Deeg and Roxane L. Degroote
Int. J. Mol. Sci. 2022, 23(17), 9555; https://doi.org/10.3390/ijms23179555 - 23 Aug 2022
Cited by 4 | Viewed by 2000
Abstract
In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this [...] Read more.
In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648. Full article
(This article belongs to the Special Issue Molecular and Immunological Approaches in Ophthalmology: Inflammatory Disorders)
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16 pages, 3008 KiB  
Article
Photoreceptor Cells Constitutively Express IL-35 and Promote Ocular Immune Privilege
by Cheng-Rong Yu, Manoj Kumar Yadav, Minkyung Kang, Yingyos Jittayasothorn, Lijin Dong and Charles E. Egwuagu
Int. J. Mol. Sci. 2022, 23(15), 8156; https://doi.org/10.3390/ijms23158156 - 24 Jul 2022
Cited by 7 | Viewed by 2869
Abstract
Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, [...] Read more.
Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, we generated IL-35/YFP-knock-in reporter mice (p35-KI) and demonstrated that photoreceptor neurons constitutively secrete IL-35, which might protect the retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse, which is hemizygous at the il12a locus, develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1/Th17 lymphocytes into the retina were preceded by a dramatic decrease of IL-35, attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in the retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege. Full article
(This article belongs to the Special Issue Molecular and Immunological Approaches in Ophthalmology: Inflammatory Disorders)
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