Intravitreal injection of dispase causes retinal hemorrhages in rabbit and human eyes

Jorge, Rodrigo; Oyamaguchi, Emerson Kenji; Cardillo, J.A.; Gobbi, Angélica; Laicine, Eduardo Miguel; Haddad, Antônio

doi:10.1076/ceyr.26.2.107.14516

Cited by 36 publications

(19 citation statements)

References 10 publications

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“…20 In rabbit eyes in vivo and in human eyes 15 min before enucleation, intravitreal injection of dispase caused intraretinal haemorrhages and ILM disruption at bleeding sites. 22 In this series, there was no effect of dispase on PVD induction.…”

Section: Hyaluronidasementioning

confidence: 60%

“…20 The enzyme has been shown to effectively induce PVR in rabbits in a dosedependent fashion, known as the dispase model of PVR, and future studies need to investigate the safety of dispase before clinical studies can be considered. 22,23 Plasmin Plasmin is a non-specific serine protease mediating the fibrinolytic process. It acts also on a variety of glycoproteins including laminin and fibronectin, both of which are present at the vitreoretinal interface.…”

Section: Hyaluronidasementioning

confidence: 99%

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Enzymatic vitreous disruption

Gandorfer

2008

Eye

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Enzymatic vitreous disruption refers to cleaving the vitreoretinal junction by enzymatic means, thereby inducing posterior vitreous detachment (PVD) and liquefaction of the vitreous gel. Several enzymes have been proposed in this respect, including chondroitinase, hyaluronidase, dispase, and plasmin. In an experimental setting, chondroitinase induced PVD and was helpful in removing epiretinal membranes but no further data have been reported yet.Hyaluronidase liquefies the vitreous as demonstrated in a phase III trial in diabetic patients with vitreous haemorrhage. Dispase induces PVD but also causes inner retinal damage and is now used as an animal model of proliferative vitreoretinopathy. Plasmin has the capability of both PVD induction and liquefaction. However, plasmin is highly unstable and not available for clinical use. Microplasmin (ThromboGenics Ltd, Dublin, Ireland) is a truncated form of human plasmin sharing the same catalytic activity like plasmin. Recombinant microplasmin is under clinical investigation in patients with vitreomacular traction. This review article reports on the current knowledge of enzymatic vitreous disruption and discusses details of the enzyme candidates in basic and clinical research terms.

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Section: Hyaluronidasementioning

confidence: 60%

Section: Hyaluronidasementioning

confidence: 99%

Enzymatic vitreous disruption

Gandorfer

2008

Eye

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“…Not only would this facilitate surgery, but it may prevent disease if performed early in the natural history. Various pharmacologic vitreolysis agents have been tested to date, [21][22][23][24][25][26][27][28][29] but little is known about the exact mechanism of action of these substances, and so far none has met with sufficient success to result in widespread use. Plasmin has been used only in limited series of uncontrolled clinical testing (two published series of nine and seven cases), chondroitinase was used only on 20 patients in a Phase I FDA trial, and hyaluronidase has recently failed a Phase III FDA trial.…”

Section: Pharmacologic Vitreolysismentioning

confidence: 99%

“…Dispase is an interesting case in point. Although two pig studies 24,28 initially showed efficacy and safety, the results of a more extensive recent study 29 in rabbit and human eyes found that dispase caused retinal toxicity, perhaps due to the broad range of proteins subject to its enzyme action. Thus, rather than employing a single broad-acting substance such as microplasmin or dispase, a combination of highly specific agents, such as collagenase, hyaluronidase, or chondroitinase, may be safer and more effective.…”

Section: Figure 17mentioning

confidence: 99%

Molecular biology of pharmacologic vitreolysis

Sebag¹

2006

American Journal of Ophthalmology

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“…No entanto, estudos realizados pelo nosso grupo em animais e humanos, constataram a ocorrência de hemorragias retinianas nas doses relatadas no trabalho original de Tezel et al A presença de hemorragias sugere que a dispase também é capaz de digerir a membrana basal dos capilares da retina, não sendo específica para os componentes da junção vítreo-retiniana (17) .…”

Section: -Dispaseunclassified

Vitrectomia farmacológica e descolamento do vítreo posterior

Oliveira¹,

Jorge²,

Costa³

et al. 2004

Arq. Bras. Oftalmol.

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Vitrectomia farmacológica e descolamento do vítreo posteriorO vítreo exerce papel crucial na patogênese de vários distúrbios vitreoretinianos. As alterações moleculares e estruturais fisiológicas do gel vítreo evoluem para a liquefação e culminam com o descolamento do córtex vítreo posterior (DVP). A ocorrência do descolamento do vítreo posterior influencia positivamente o prognóstico de pacientes diabéticos, com maculopatias e vasculopatias. Abordaremos o conceito da vitrectomia farmacológica que se refere ao uso de agentes que alteram a organização molecular do vítreo, num esforço de reduzir ou eliminar seu papel na gênese de doenças vítreo-retinianas, sendo o seu objetivo final, o descolamento total do vítreo posterior. Vários agentes têm sido estudados durante a última década, porém, existem várias limitações na aplicabilidade clínica destes compostos. Nesse artigo de revisão, iremos abordar os diferentes agentes e os seus mecanismos de ação sobre a matriz extracelular e a interface vítreo-retiniana. INTRODUÇÃODescolamento do vítreo posterior (DVP) pode ser definido como a separação da região cortical do vítreo posterior da membrana limitante interna da retina (MLI). Pesquisas realizadas a partir de necrópsias relatam a incidência de DVP em 63% dos olhos estudados na oitava década de vida (1) . O DVP é mais comum em mulheres e em míopes, ocorrendo dez anos mais cedo nestes casos do que em emétropes e hipermétropes. A cirurgia de catarata também pode abreviar o aparecimento de DVP, principalmente em pacientes míopes (2) .O DVP resulta do enfraquecimento da adesão do córtex vítreo com a MLI, em conjunto com a liquefação vítrea que ocorre com o avanço da idade. Ao processo de liquefação vítrea denominamos sínquise. Postula-se que o vítreo liquefeito atinja o espaço posterior ao córtex vítreo através de uma abertura deste, localizada na região imediatamente anterior ao disco óptico (área de Martegiani) (3) . Com o movimento do corpo e conseqüente-mente da cabeça e dos olhos, o vítreo liquefeito vagarosamente disseca o espaço retro-cortical, aumentando a área de descolamento do córtex vítreo da MLI. O DVP acontece, então, quando a adesão vítreo-retiniana é rompida, havendo um colapso do corpo vítreo totalmente separado da retina, em um processo denominado de sinérese (4) .O DVP total caracteriza-se pela completa separação entre o vítreo cortical posterior e a retina (sem áreas residuais de adesão em superfície retiniana). A ocorrência do DVP total em pacientes com vasculopatias da retina ATUALIZAÇÃO CONTINUADA

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Intravitreal injection of dispase causes retinal hemorrhages in rabbit and human eyes

Abstract: Retinal hemorrhages were evident as early as 11 min after injection. It is suggested that this enzyme degraded selectively basement membrane components without affecting other proteins involved in the vitreous-retinal junction.

Cited by 36 publications

References 10 publications

Enzymatic vitreous disruption

Enzymatic vitreous disruption

Molecular biology of pharmacologic vitreolysis

Vitrectomia farmacológica e descolamento do vítreo posterior

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