Induction of Posterior Capsule Opacification by Hyaluronic Acid in an Ex Vivo Model

Chandler, Heather L.; Haeussler, David J.; Gemensky-Metzler, Anne J.; Wilkie, David A.; Lutz, Elizabeth A.

doi:10.1167/iovs.11-8735

Cited by 23 publications

(24 citation statements)

References 62 publications

(87 reference statements)

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“…This experimental model has also provided insight into the mechanisms of PCO and better management of the problem. For example, hyaluronic acid which is found in viscoelastics, commonly used in cataract surgery, was found to promote cell proliferation across the posterior capsule (Chandler et al, 2012). In addition, it has been found that pharmacological inhibition of cyclooxygenase-2 could reduce cell migration promote apoptosis and suppress transdifferentiation (Davis et al, 2012).…”

Section: Caninementioning

confidence: 99%

Experimental models for posterior capsule opacification research

Wormstone

Eldred

2016

Experimental Eye Research

104

102

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Millions of people worldwide are blinded due to cataract formation. At present the only means of treating a cataract is through surgical intervention. A modern cataract operation involves the creation of an opening in the anterior lens capsule 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 the entire posterior capsule. In most cases, an intraocular lens is implanted into the capsular bag during surgery. This procedure initially generates good 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, including hyperproliferation, migration, matrix deposition, matrix contraction and transdifferentiation into myofibroblasts. These changes alone can cause visual deterioration, but in a significant number of cases, fibre differentiation is also observed, which gives rise to Soemmering's ring and Elschnig's pearl formation. Elucidating the regulatory factors that govern these events is fundamental in the drive to develop future strategies to prevent 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 research and provide examples of key findings that have resulted from these approaches.

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Section: Caninementioning

confidence: 99%

Experimental models for posterior capsule opacification research

Wormstone

Eldred

2016

Experimental Eye Research

104

102

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“…Estudo realizado anteriormente em humanos evidenciou que há aumento na expressão de proteínas na membrana extracelular das cápsulas colhidas de pacientes diabéticos, quando comparados às colhidas de pacientes sadios que apresentavam apenas cataratas do tipo corticais, o que supostamente poderia alterar a composição dos proteoglicanos nessa estrutura e, por consequência, sua função nestes pacientes (Tiwari et al 2014). Outros estudos referem que há uma maior produção de colágeno na presença de catarata e/ou diabete e que a alteração é ainda maior no grupo dos diabéticos, quando também comparados a pacientes sadios (Glover & Constantinescu 1997, Bras et al 2006, Pot et al 2009, Wormstone et al 2009, Chandler et al 2012. Diferente dos referidos estudos, não se observou diferença significante quanto ao aumento na expressão de proteínas (proteoglicanos) e/ou colágeno entre os grupos estudados.…”

Section: Discussionunclassified

Avaliação da composição molecular da cápsula anterior da lente de cães idosos com catarata de alto risco

et al. 2016

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Resumo: Atualmente, a cápsula anterior e o epitélio da lente tem sido cada vez mais estudados, com o intuito de reduzir as possíveis complicações do pós-operatório da remoção da catarata, tal como a opacidade da cápsula posterior, alteração ocasionada principalmente pela diferenciação e migração das células do epitélio lenticular para a cápsula posterior da lente. O objetivo deste estudo foi analisar a composição molecular da cápsula anterior da lente pela técnica histoquímica de PAS (avaliação de proteoglicanos) e picrosirius red (avaliação de colágeno IV), em cães idosos com catarata diabética e não diabética do tipo hipermadura, submetidos ao uso ou não de azul de tripano a 0,1 % durante a facoemulsificação. Vinte e sete cães foram estudados, incluindo 21 fêmeas e 6 machos, de 8 a 12 anos de idade (média = 9,6 anos), de diversas raças e divididos em 2 grupos: GC (catarata hipermadura) e GCD (catarata diabética). Os resultados das análises realizadas mostraram que ambas as amostras, tanto as provenientes das cataratas hipermaduras, quanto das diabéticas, apresentam semelhante composição molecular de proteoglicanos e colágeno IV e isto independente da utilização de azul de tripano a 0,1 %. Conclui-se, portanto, que se os resultados obtidos forem decorrentes de alterações provocadas pelo rápido metabolismo da catarata diabética e pela cronicidade da catarata hipermadura sugere-se que o comprometimento da estrutura capsular seja de intensidade equivalente e, por consequência, que isto também possa prejudicar o metabolismo das células do epitélio anterior da lente, diminuindo assim a incidência da opacidade da cápsula posterior de cães com catarata diabética e hipermadura submetidos à facoemulsificação.

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“…Sham cataract surgery was performed on harvested globes, as previously described . Briefly, scissors were used to excise the cornea from the globe and the iris was incised at its base and removed, exposing the anterior lens.…”

Section: Methodsmentioning

confidence: 99%

Determination of trypan blue efficacy in the mitigation of ex vivo canine PCO formation

Brash

Gemensky-Metzler

Wilkie

et al. 2019

Veterinary Ophthalmology

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Purpose:To determine whether trypan blue (TB) reduces canine lens epithelial cell (LEC) or corneal endothelial cell (CEC) viability in vitro; if cell death is noted, to subsequently evaluate the molecular mechanism. Methods: Cellular viability was determined using a lactate dehydrogenase (LDH) assay. In TB-treated LECs, caspase 3/7 activity was assessed to evaluate apoptosis; autophagy was evaluated using immunoblotting against LC3 and p62. To evaluate the effects of TB on ex vivo posterior capsule opacification (PCO), following mock cataract surgery, lens capsules were treated with TB and subsequently maintained in culture to determine LEC migration and proliferation. Results: Following acute exposure, TB did not significantly reduce LEC or CEC viability at any of the concentrations tested. Increased caspase 3/7 activity was found in LEC cultures treated with TB for an extended period of time; no change in LC3 or p62 expression was noted. Ex vivo PCO formation was not significantly altered by TB treatment. Conclusions: Acute exposure to TB did not reduce LEC or CEC viability, and only longer exposure to TB was able to initiate apoptosis. Treatment with intraocular TB at the time of cataract surgery is likely safe to the CECs but will not prevent PCO formation. K E Y W O R D S apoptosis, autophagy, corneal endothelial cells, cytotoxicity, posterior capsule opacification, vital dye How to cite this article: Brash BM, Gemensky-Metzler AJ, Wilkie DA, Miller EJ, Chandler HL. Determination of trypan blue efficacy in the mitigation of ex vivo canine PCO formation. Vet Ophthalmol. 2019;22:902-909. https://doi.

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Induction of Posterior Capsule Opacification by Hyaluronic Acid in an Ex Vivo Model

Abstract: Exogenous HA can induce lenticular migration and CD44 expression. Use of surgical viscoelastics that contained HA resulted in increased rates of ex vivo PCO suggesting that judicious selection and use of viscoelastic material during cataract surgery is warranted.

Cited by 23 publications

References 62 publications

Experimental models for posterior capsule opacification research

Experimental models for posterior capsule opacification research

Avaliação da composição molecular da cápsula anterior da lente de cães idosos com catarata de alto risco

Determination of trypan blue efficacy in the mitigation of ex vivo canine PCO formation

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