Using Current Data to Define New Approach in Age Related Macular Degeneration: Need to Accelerate Translational Research

Anand, Akshay; Sharma, Kaushal; Chen, Wei; Sharma, Neel

doi:10.2174/1389202915666140516204512

Cited by 10 publications

(9 citation statements)

References 82 publications

(58 reference statements)

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“…Diseases affecting the posterior segment of the eye are devastating and cause blindness in many patients. In recent decades, highly developed countries have witnessed a dramatic increase in the incidence of such pathologies, especially in those which are age-related (Anand 2014). These include uveitis (Miserocchi 2013), proliferative diabetic retinopathy (Sapieha 2010), macular oedema (Zhang 2014) and macular degeneration associated with age (AMD) (van Wijngaarden 2008).…”

Section: Introductionmentioning

confidence: 99%

Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration

Villanueva

Bravo‐Osuna

Herrero-Vanrell

et al. 2016

European Journal of Pharmaceutical Sciences

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Successful therapy for chronic diseases affecting the posterior segment of the eye requires sustained drug concentrations at the site of action for extended periods of time. To achieve this, it is necessary to use high systemic doses or frequent intraocular injections, both associated with serious adverse effects. In order to avoid these complications and improve patient's quality of life, an experimental study has been conducted on the preparation of a new generation of biodegradable poly(D,L-lactide-co-glycolide) (50:50) (PLGA) polymer microspheres (MSs) loaded with Dxm, vitamin E and/or human serum albumin (HSA). Particles were prepared according to a S/O/W encapsulation method and the 20-40μm fraction was selected. This narrow size distribution is suitable for minimally invasive intravitreal injection by small calibre needles. Characterisation of the MSs showed high Dxm loading and encapsulation efficiency (> 90%) without a strong interaction with the polymer matrix, as revealed by DSC analysis. MSs drug release studies indicated a small burst effect (lower than 5%) during the first five hours and subsequently, drug release was sustained for at least 30days, led by diffusion and erosion mechanisms. Dxm release rate was modulated when solid state HSA was incorporated into MSs formulation. SDS-PAGE analysis showed that the protein maintained its integrity during the encapsulation process, as well as for the release study. MSs presented good tolerance and lack of cytotoxicity in macrophages and HeLa cultured cells. After 12months of storage under standard refrigerated conditions (4±1°C), MSs retained appropriate physical and chemical properties and analogous drug release kinetics. Therefore, we conclude that these microspheres are promising pharmaceutical systems for intraocular administration, allowing controlled release of the drug.

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Section: Introductionmentioning

confidence: 99%

Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration

Villanueva

Bravo‐Osuna

Herrero-Vanrell

et al. 2016

European Journal of Pharmaceutical Sciences

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“…Neovascularization underlying choroid can percolate the Bruch’s membrane and disrupt the integrity of retinal pigment epithelium (RPE) layer. Neovascularization process is guided by several angiogenic factors including Platelet-derived growth factor (PDGF) 1 , 2 , matrix metalloproteinases (MMPs), 3 , 4 Pigment epithelium-derived factor (PEDF) 5 , TGF-β and its receptors. 6 , 7 Among all, vascular endothelial growth factor (VEGF) is more potent to lead angiogenic process.…”

Section: Introductionmentioning

confidence: 99%

“…Although, it has been found that TGF-β could induce the VEGF expression in RPE cells, with the involvement of MAP kinases, signifies the role of TGF beta as the pro-angiogenic protein in enabling angiogenic process. 8 Apart from these angiogenic factors, several pro-angiogenic factors (TIMPs family and FGF) 3 , 4 are also involved in the process. Hence, neovascularization is a complex process having role of both angiogenic and pro-angiogenic factors.…”

Section: Introductionmentioning

confidence: 99%

Exploring the role of VEGF in Indian Age related macular degeneration

Sharma

Singh

et al. 2015

ANS

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BackgroundAge related macular degeneration (AMD) is major devastating neurodegenerative disorder characterized by progressive irreversible vision loss in the elderly persons. In spite of several genetic and environmental factors, the role of VEGF and CFH predispose the pathological phenomenon in the AMD patients.PurposeThe aim of the study was to estimate the VEGF levels in the serum of AMD patients and its correlation with co-morbidity of the participants.MethodsThe study recruited the 98 AMD patients and 59 controls with proper consent of the participants as per the exclusion-inclusion criteria. The co-morbidity and socio-economic details were obtained by introducing the standard questionnaire amongst the participants. Serum levels of vascular endothelial growth factor (VEGF) was estimated by ELISA and compared with the control population of the study. The levels of VEGF in the serum of AMD patients and controls were compared with Mann-Whitney U-test. Kruskal Wallis one-way analysis of variance (ANOVA) was employed to analyze more than two variables in the study.ResultsElevated level of VEGF was found in AMD patients as compared to controls. Surprisingly, we did not find significant changes among wet AMD subtypes i.e. minimal, predominant and classic wet AMD. However, we have demonstrated the intravitreal anti-VEGF treatment (avastin) in AMD patients could reduce the systemic VEGF levels although it was not significant. Moreover, the heart ailment in the AMD patients could also influence the VEGF levels.ConclusionOur study is consistent with previous studies describing the imperative significance of VEGF in AMD pathology. However, our study did not reveal the role of VEGF in wet AMD progression but it is well established causative agent for the same. The increased levels of VEGF in heart ailment among AMD patients are significant.

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“…The reason for this is not ignorance or reluctance of ophthalmologists, but rather the lack of translational studies transferring the genomic findings from basic research to clinical research, and from there to evidence-based recommendations for implementation in practice [47]. Anand et al describe that although the number of population-based genetic studies in AMD is increasing every year, most of these findings have not been translated into development of human diagnostic, prognostic and pharmaceutical applications [48]. For example, future studies may investigate whether individuals tested for AMD genes have a lower risk of developing the manifest disease when adhering to a preventive lifestyle, and whether knowing their risk affects their quality of life.…”

Section: Discussionmentioning

confidence: 99%

Views of ophthalmologists on the genetics of age-related macular degeneration: Results of a qualitative study

et al. 2018

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BackgroundAge-related macular degeneration (AMD) is the leading cause of blindness in industrialized countries. It is a multifactorial disease of the retina modified by environmental/individual (e.g. smoking) and genetic factors. 34 independent genomic loci are associated with the risk to develop AMD; an interaction between smoking and genetics is currently investigated. It is unclear how the knowledge on the strong genetic component has entered the knowledge base of practicing ophthalmologists, and how they inform and counsel their (AMD) patients about it. In this study, we explore the ophthalmologists’ view on AMD genetics, and their inclination towards communicating genetic risks to patients.MethodsWe recruited a purposive sample of thirty German ophthalmologists (office based: n = 15, hospital employees: n = 15, f:8/30), who took part in a recorded semi-standardized interview. Transcripts were analyzed using content analysis.ResultsThe majority of office-based ophthalmologists claimed to be unfamiliar with genetics of AMD, in contrast to hospital-affiliated ophthalmologists. Both office and hospital ophthalmologists were convinced that genetics lacks practical relevance in everyday patient care. Many withhold information on heritability or genetic background of AMD from patients and their relatives, for fear of unsettling those individuals. The relevance of the genetic component of AMD or an individuals’ high genetic risk for prevention, e.g. screening or lifestyle modifications in persons with adverse genetic profile, was rated low.ConclusionDeveloping genetic educational programs tailored to the routine care of ophthalmologists may be indicated, as well as a better two-way communication between research and practice. Exploring patient views about their expectations to being informed about genetic disease etiology, or about their individual risk, would help inform communication strategies.

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Using Current Data to Define New Approach in Age Related Macular Degeneration: Need to Accelerate Translational Research

Cited by 10 publications

References 82 publications

Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration

Optimising the controlled release of dexamethasone from a new generation of PLGA-based microspheres intended for intravitreal administration

Exploring the role of VEGF in Indian Age related macular degeneration

Views of ophthalmologists on the genetics of age-related macular degeneration: Results of a qualitative study

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