Ahmed M. Abu El-Asrar

John Christoforidis

Mario R. Romano

Mediators of Inflammation

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Hindawi Publishing CorporationMediators of In�ammationVolume 2013, Article ID 758035, 2 pageshttp://dx.doi.org/10.1155/2013/758035Editorial�ntra�itreal �n�ammation� �rom �en�hside to �edsideMario R. Romano,1 John Christoforidis,2 and AhmedM. Abu El-Asrar31 Department of Ophthalmology, Istituto Clinico Humanitas, Rozzano, 20089 Milan, Italy2Department of Ophthalmology, College of Medicine, e University of Arizona, Tucson, AZ 85711, USA3Department of Ophthalmology, College of Medicine, King Saud University, Riyadh 11451, Saudi ArabiaCorrespondence should be addressed to Mario R. Romano; romanomario@email.itReceived 16 December 2012; Accepted 16 December 2012Copyright © 2013 Mario R. Romano et al. is is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.In�ammation plays a ma�or role in the formation and in theprogression of sight-threatening chorioretinal diseases suchas diabetic retinopathy (DR), proliferative vitreoretinopa-thy (PVR), uveitis, and age-related macular degeneration(AMD). A greater understanding of the underlying patho-logical mechanisms is necessary for the development ofbetter therapeutic agents and relies on the analysis of clinicalspecimens as well as on animal models. Contrary to theretina, the vitreous humour (VH) is a transparent gel that �llsthe posterior chamber of the eye and can be sampled withoutcausing visual loss. In recent years, advances in the analysisof VH samples have highlighted new biological mechanismsof long-known diseases and have improved the accuracy ofdiagnostic procedures.In this special issue, we report how the VH �ndings at thebenchside can be translated to the bedside, and how this mayhelp clinical practice. e papers have been contributed by anumber of experts in the �eld and include both review articlesthat provide an overview of the work conducted to date,as well as original articles reporting recent discoveries andinnovations. In order to highlight the translational relevanceof VH analyses, most of the papers are focused on a speci�cdisease entity. We hope that this series of manuscripts willbe bene�cial for clinicians in their diagnostic and therapeuticapproaches towards intravitreal in�ammatory conditions andfor researchers in appreciating some of the recent innovationsand their clinical implications in this �eld. Each of themanuscripts in this series is brie�y highlighted as follows.e paper by M. Angi et al. “Proteomic analyses of thevitreous humour” describes how to correctly collect andhandle VH specimens and presents a clear work�ow forproteomic analyses. is is signi�cant since the VH is nota straightforward tissue to analyze due to its viscous con-sistency. Proteomic technologies have dramatically evolvedover the past years, allowing identi�cation of an increasingnumber of disease-speci�c proteins in the VH. Moreover,recent proteomic studies on the VH from animal models ofautoimmune uveitis have highlighted new pathways associ-ated to autoimmune triggers and intravitreal in�ammationthat could become the targets for much needed therapies.Another example of the usefulness of proteomic analysesof the VH in translational research is presented by O. Simó-Servat et al. in “Usefulness of the vitreous �uid analysis inthe translational research of diabetic retinopathy” who applied�uorescence-based di�erence gel electrophoresis (DIGE), aswell as �ow cytometry, to identify new candidates involvedin the in�ammatory process that occurs in DR. e authorsprovide evidence supporting the role of proin�ammatorymediators such as cytokines (i.e., IL-1𝛽𝛽, IL-6, IL-8, andTNF𝛼𝛼), chemokines (i.e., MCP-1, SDF-1, and IP-10), andadhesionmolecules (i.e., VCAM, ICAM-1, andVAP-1) in thepathogenesis of DR. Such persistent low-grade in�ammationcontributes to the damage of the internal blood-retinalbarrier and to the development of proliferative diabeticretinopathy (PDR).A. M. Abu El-Asrar et al. in “Osteopontin and otherregulators of angiogenesis and �brogenesis in the vitreousfrom patients with proliferative vitreoretinal disorders” and“High-mobility group box-1 and endothelial cell angiogenicmarkers in the vitreous from patients with proliferative dia-betic retinopathy” investigate the role of osteopontin andother regulators of angiogenesis and �brogenesis, such ashigh-mobility group box-1 (HMGB1) and connective tissuegrowth factor (CTGF) in the pathogenesis of proliferative2 Mediators of In�ammationvitreoretinal disorders with a concomitant increase of anti�-brogenic pigment epithelium-derived factor (PEDF) levels inthe VH. Moreover, the authors report that HMGB1, solublevascular endothelial-cadherin (sVE-cadherin), and solubleendoglin (sEng) regulate the angiogenesis of endothelial cellsin PDR.R. dell’Omo et al. in “Vitreous mediators in retinal hypoxicdisease” describe that serum adiponectin (APN) levels cor-relate with blood in�ammatory marker levels and with DRas response to endothelium dysfunction, indicating the roleof APN as endogenous modulator of microvascular functionand in�ammation.S. N. Moysidis et al. in “Mechanisms of in�ammationin proliferative vitreoretinopathy: from bench to bedside”describe the indirect activation of PDGFR𝛼𝛼 by non-PDGFsas trigger that leads to development of PVR. In this pathway,the intracellular reactive oxygen species (ROS) plays a keyrole, leading to activation of Src family kinases (SFKs) thatpromote phosphorylation and activation of PDGFR𝛼𝛼. eROS could be one of the therapeutic targets of multimodalapproach.D. Gologorsky et al. in “erapeutic interventions againstin�ammatory and angiogenic mediators in proliferative dia-betic retinopathy” report the latest focus of targeted therapiesfor proliferative diseases through the block of vascular adhe-sion molecules such as ICAM-1, VCAM-1, in�ammatoryfactors including the interleukins, tumor necrosis factor(TNF), insulin-like growth factor (IGF), and angiopoietins(Ang-2).Analysis of the VH is a valuable adjunct also for themanagement of patients with uveitis and especially in thediagnosis of neoplastic diseases masquerading as chronicintraocular in�ammation, as reported by E. M. Damato etal. in “Vitreous analysis in the management of uveitis.” Forexample, increased levels of T-cell cytokine, IL-6, in VHis characteristic of uveitis, whereas increased levels of IL-10 and in particular IL-10/IL-6 ratio greater than 1 shouldprompt cytological analysis for the diagnosis of vitreoretinallymphoma.e involvement ofVH in neoplastic diseases andthe pros and cons of performing VH biopsies in the clinicalpractice are further discussed in the review article by M.Asencio-Duran et al. entitled “Vitreous diagnosis in neoplasticdiseases.”J. L. Vallejo-Garcia et al. in “Role of in�ammation inendophthalmitis” discuss the role of in�ammation in infectiveendophthalmitis, reporting that the damage to the retina inthis rare but severe diseases is mediated by the host immunereaction through toll-like receptors, cytokines, HMGB1, andaB-crystallin. A better understanding of the host immunereaction and the cellular pathways leading to tissue damageis also essential to improve clinical outcomes. Corticosteroidsare frequently administered with antibiotics but oen donot fully control the host immune reaction with consequentvisual loss. A novel TLR2 ligand, Pam3Cys, has demonstratedencouraging results when administrated before the onset ofendophthalmitis and also when injected in combination withintravitreal antibiotics.J. B. Christoforidis et al. in “Intravitreal devices for thetreatment of vitreous in�ammation” describe the importanceof the modulation of pharmacokinetics in the treatment ofchronic intraocular in�ammation. Long-term treatments arecurrently provided by drug-delivery devices, which includenonbiodegradable and biodegradable devices. e therapeu-tic agents that can be delivered are ganciclovir, �uocinoloneacetonide, triamcinolone acetonide, and dexamethasone.enext small-scale biodegradable devices already described areliposomes, microspheres, and nanoparticles from 0.01 to1,000 𝜇𝜇m in diameter.J. B. Christoforidis et al. in “Systemic treatment of vitreousin�ammation” also report thatmany classes of systemic drugsmay be used alone or in combination to control intraocularin�ammation while closely monitoring side eﬀects. Many ofthese in�ammatory disorders require long-term treatment,and hence steroid-sparing agents, including antimetabolites,alkylating agents, and biological agents, are being used.e emerging topic of sterile endophthalmitis is pre-sented by J. Marticorena et al. in “Sterile endophthalmitis aerintravitreal injections.” It is an infrequent complication ofintravitreal injections and seems to develop in the context ofthe oﬀ-label use of drugs that have not been conceived forintravitreous administration. Sterile in�ammation secondaryto IVTAand IVB sharemany characteristics, such as the acuteand painless vision loss present in the vast majority of thecases.In�ammation also plays a major role also in the agingretina, where free radicals and oxidized lipoproteins areconsidered to be major causes of tissue stress. F. Parmeggianiet al. in “Mechanism of in�ammation in age-related maculardegeneration” report that the consequence is a parain�am-mation, a chronic status which contributes to initiationand progression of neurodegenerative diseases such as age-relatedmacular degeneration (AMD).e parain�ammatoryderegulation that is already present in the early stage ofAMD may notionally support the preventive employment ofagents directed against the immune-in�ammatory responsein combination with high-dose nutritional supplements.We sincerely hope that the present special issue mayprovide useful information to understand the mechanisms,the clinical eﬀects, and the novel treatments of in�ammationin which the vitreous is involved.Mario R. RomanoJohn ChristoforidisAhmed M. 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Intravitreal Inflammation: From Benchside to Bedside

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Intravitreal Inflammation: From Benchside to Bedside

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