Wormstone_and_Eldred_2014_revision_3_29_April_2015
➤ Gửi thông báo lỗi ⚠️ Báo cáo tài liệu vi phạmNội dung chi tiết: Wormstone_and_Eldred_2014_revision_3_29_April_2015
Wormstone_and_Eldred_2014_revision_3_29_April_2015
Experimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015f East Anglia.Norwich.NR4 7TJUK‘Corresponding author - E-mail: i.m.wormstone@uea.ac.ukRunning title: Models for PCOKey words: Posterior Capsule Opacification: Models: Lens: fibrosis: wound-healing11.AbstractMillions of people worldwide are blinded due to cataract formation. At present the only means Wormstone_and_Eldred_2014_revision_3_29_April_2015 of treating a cataract is through surgical intervention. A modern cataract operation involves the creation of an opening in the anterior lens capsuleWormstone_and_Eldred_2014_revision_3_29_April_2015
to allow access to the fibre cells, which are then removed. This leaves in place a capsular bag that comprises the remaining anterior capsule and theExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015od visual restoration, but unfortunately, residual lens epithelial cells undergo a wound-healing response invoked by surgery, which in time commonly results in a secondary loss of vision. This condition is known as posterior capsule opacification (PCO) and exhibits classical features of fibrosis, in Wormstone_and_Eldred_2014_revision_3_29_April_2015cluding hyperproliferation, migration, matrix deposition, matrix contraction and transdifferentiation into myofibroblasts. These changes alone can cauWormstone_and_Eldred_2014_revision_3_29_April_2015
se visual deterioration, but in a significant number of cases, fibre differentiation is also observed, which gives rise to Soemmering’s ring and ElschExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015 or delay visual deterioration resulting from PCO. A range of experimental platforms are available for the study of PCO that range from in vivo animal models to in vitro human cell and tissue culture models. In the current review, we will highlight some of the experimental models used in PCO researc Wormstone_and_Eldred_2014_revision_3_29_April_2015h and provide examples of key findings that have resulted from these approaches.22.IntroductionFibrosis is a condition that affects multiple organs anWormstone_and_Eldred_2014_revision_3_29_April_2015
d is associated with hyperproliferation, migration, matrix deposition, matrix contraction and transdifferentiation into myofibroblasts (Leask and AbraExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015 in virtually all cases (Eldred et al., 2011; Wormstone, 2002; Wormstone et al., 2009). In a number of patients, fibre differentiation IS also evident, which gives rise to Soemmering's ring and Elschnig's pearls that can cause further visual deterioration (Findl et al.. 2010; van Bree et al., 2013a; Wormstone_and_Eldred_2014_revision_3_29_April_2015 van Bree et al., 2012). PCO affects millions of individuals (Eldred et al., 2011; Wormstone, 2002; Wormstone et al., 2009). Understanding the regulatWormstone_and_Eldred_2014_revision_3_29_April_2015
ory mechanisms that underpin this condition IS crucial if we are to advance treatment strategies that will prevent or delay visual deterioration resulExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015m of PCO and highlight some of the experimental platforms available for PCO research and provide examples of key findings that have resulted from these approaches.Cataract is the major priority in the global initiative to eliminate avoidable blindness by the year 2020 (McCarty and Taylor. 2001). Due Wormstone_and_Eldred_2014_revision_3_29_April_2015 to medical and sociological advances we are in a time where longevity has been significantly extended and our ageing population is increasing (ht(p:/Wormstone_and_Eldred_2014_revision_3_29_April_2015
/www.worldometers.info/world-population/). Consequently, the incidence of cataract will rise. Cataract surgery is already the most common operative prExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015ults, It is blighted by a secondary loss of vision caused by PCO, which3requires further surgical intervention to restore vision in a patient. This affects the wellbeing of the individual and places a great financial burden on health care providers (Wormstone et al., 2009).A modern cataract operatio Wormstone_and_Eldred_2014_revision_3_29_April_2015n involves making a small incision in the sclera or cornea to permit introduction of surgical tools with minimal physical disruption to the eye. An opWormstone_and_Eldred_2014_revision_3_29_April_2015
ening in the lens is made by creating a continuous curvilinear capsulorhexis (capsular tear) in the anterior capsule using a capsulotome; an alternatiExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015s circular window in the anterior capsule allows access to the central regions of the lens that are typically associated with cataractous change. The lens fibres are usually removed by phacoemulsification, but in some cases this is assisted by femtosecond laser treatment of the fibre cells and on ra Wormstone_and_Eldred_2014_revision_3_29_April_2015re occasions traditional hydrodissection methods are required. Residual fibre cells are removed by irrigation/aspiration techniques. The product of caWormstone_and_Eldred_2014_revision_3_29_April_2015
taract surgery is a capsular bag; which comprises a portion of the anterior and the entire posterior capsule. The bag remains within the eye and is suExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015(IOL) is placed within the capsular bag and in doing so restores refractive power. Following surgery light can pass freely along the visual axis through the transparent IOL and thin acellular posterior capsule. However, lens epithelial cells can resist the trauma of surgery and these robust cells in Wormstone_and_Eldred_2014_revision_3_29_April_2015 time re-colonise regions of the anterior capsule denuded by surgical abrasion. Most importantly cells colonise the previously cell-free posterior capWormstone_and_Eldred_2014_revision_3_29_April_2015
sule and encroach upon the visual axis. Modifications to cell organisation and the underlying matrix can cause light scatter (van Bree et al.,42013b; Experimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015l posterior capsule and associated cells, in order to permit an uninterrupted path through the visual axis (Wormstone et al.. 2009); however this is both expensive, logistically difficult with elderly patients and has associated medical risk, such as increased likelihood of retinal detachment (Ranta Wormstone_and_Eldred_2014_revision_3_29_April_2015 and Kivela, 1998).There are a number of factors that can increase the incidence of PCO, for example young age. intraocular inflammation and surgicalWormstone_and_Eldred_2014_revision_3_29_April_2015
factors (Wormstone et al.. 2009). Many studies have shown that PCO rates can be diminished by improved IOL design (Hayashi et al.. 2001; Nishi et al..Experimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015ll require a Nd:YAG laser capsulotomy within 2 years of surgery (Li et al.. 2013) and these numbers continue to rise with greater post-surgical time (Vock et al.. 2009). This places a strain on healthcare resources, medical time and the quality of a patient s life (Cleary et al., 2007). These proble Wormstone_and_Eldred_2014_revision_3_29_April_2015ms are exacerbated in paediatric eyes, eyes with inflammation or with multifocal lOLs. Reducing the impact of PCO on patients is therefore of great prWormstone_and_Eldred_2014_revision_3_29_April_2015
actical importance and novel approaches need to be developed.Our understanding of the biological processes governing PCO formation (figure 2) and how Experimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015us scientists and clinicians need to gather, interpret and apply information that furthers our understanding of PCO and its management. In order to achieve this, a body of5experimental systems are required and should be viewed as a collection of tools that together can best answer key questions. PCO Wormstone_and_Eldred_2014_revision_3_29_April_2015 research is well served by a variety of experimental systems (Table 1). We will therefore go on to discuss developments with in vivo models, cell culWormstone_and_Eldred_2014_revision_3_29_April_2015
ture systems and tissue culture models. With respect to any model It is vital that the experimental design and objectives are ultimately directed to tExperimental Models for Posterior Capsule Opacification ResearchIan Michael Wormstone* and Julie Ann EldredSchool of Biological Sciences.University of Wormstone_and_Eldred_2014_revision_3_29_April_2015e performed in veterinary practices and again PCO is a major problem in these patients. With respect to guiding our research programmes and specific experiments it is important to examine the information provided through post-mortem analysis (Marcantonio et al.. 2000: Saika et al., 2002: Wormstone e Wormstone_and_Eldred_2014_revision_3_29_April_2015t al.. 2002a) and patient imaging systems (Grewal et al., 2008: Ursell et al., 1998). Cell organisation, modifications, expression of genes or proteinWormstone_and_Eldred_2014_revision_3_29_April_2015
s provide a snap-shot at the scene of the crime. It is. however, difficult to garner the processes that lead to these changes directly from such data.Gọi ngay
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