Inviato: Mer 24 Ago, 2005 16:54 Oggetto: Ialuronidasi
inauguro questa nuova sezione con un topic riguardante un'enzima, ialuronidasi, che in alcuni studi sperimentali è risultato non solo essere innocuo ma ha dato anche risultati incoraggianti per un futuro trattamento delle miodesopsie. riporto di seguito l'unica pubblicazione al riguardo attualmente edita.
si tratta di una sperimentazione di alcuni medici polacchi su di un coniglio affetto da mosche volanti al quale è stata praticata un'iniezione intravitreale di ialuronidasi con risultanti incoraggianti:
: Klin Oczna. 2002;104(2):135-7. Related Articles, Links
[Efficacy of hyaluronidaze in reducing vitreous opacites--preliminary report]
[Article in Polish]
Puchalska-Niedbal L, Millo B.
Katedry i Kliniki Okulistyki z Zakladem Patofizjologii Narzadu Wzroku Pomorskiej Akademii Medycznej, Szczecinie.
The aim of the work: the assessment of hyaluronidase as reducer of floaters in vitreus body. We present one patient with the floaters in vitreus body treated by subconjunctival injection with hyaluronidase. Research work was carried out on a rabbit, which had been given 10 subconjunctival injections of hyaluronidaze. After treatment we noted subjective and local improvement. By using biochemical tests we proved, that subconjunctival hyaluronidaze application is a good way, to obtain an effect in the vitreous.
A quanto pare mi tocca il ruolo di bastian contrario, eh eh eh.
Scherzo ovviamente, lo faccio solo per stimolare la discussione. Vitto sa quanto stimo i suoi post.
Anche in altre occasioni mi sono detto scettico su questo metodo.
Da un lato "liquefare" il vitreo offre indubbi vantaggi nel trattamento delle miodesopsie. In definitiva si dovrebbe arrivare a scioglierle insieme al gel vitreale stesso.
Dall'altro non si fa altro che accellerare il processo degenerativo del vitreo, rimanendo alla fine "senza" vitreo.
Ora, molti sostengono che il vitreo negli adulti non serva più. Il suo compito è quello di dare la forma all'occhio nelle fasi dello sviluppo. Ma siamo sicuri che sia solo questo il compito del vitreo? Come mai il 90% dei soggetti privati del vitreo attraverso la vitreoctomia sviluppano una cataratta? Senza contare la funzione di assorbimento degli urti.
Secondo me la vitreolisi enzimatica rimane a soluzione più promettente, ma non sono sicuro sia tutta rose e fiori.
in alcuni studi è stato dimotrato che l'enzima ialuronidasi iniettato in piccole dosi non è in grado produrre da solo la liquefazione totale del vitreo e di conseguenza un distacco posteriore del vitreo dalla retina (PVD).
secondo la mia modesta opinione l'utilizzo nella ialuronidasi nello studio soprariportato sarebbe finalizzato ad un parziale riassorbimento dei corpi mobili vitreali senza intaccare in maniera macroscopica la struttura stessa del vitreo.
tutto sta nel riuscire a individuare un giusto dosaggio. non è un caso che qualche studioso abbia prospettato l'ipotesi di un possibile impiego in futuro di un framaco molto simile al VITRASE, quindi ialuronidasi, nella cura delle miodesopsie.
PVD following plasmin but not hyaluronidase: implications for combination pharmacologic vitreolysis therapy.
Wang ZL, Zhang X, Xu X, Sun XD, Wang F.
Department of Ophthalmology, Shanghai First People's Hospital, People's Republic of China. email@example.com
PURPOSE: To study whether intravitreal injection of plasmin + hyaluronidase safely induces posterior vitreous detachment (PVD). METHODS: Rabbits were randomized into three groups: (A) 20 rabbits, intravitreal injection of plasmin 1 U + hyaluronidase 20 U in balanced salt solution (BSS) 0.1 mL into one eye; (B) 12 rabbits, plasmin alone; (C) 12 rabbits, hyaluronidase alone. The fellow eye of each rabbit was injected BSS 0.1 mL. In Group A, scanning electron microscopy (SEM) was done in four rabbits at 0.5 hour and in four rabbits at 1 hour. After 7 days, all the remaining 36 rabbits received electroretinography, SEM was examined in eight of each group, and immunohistochemistry was done in four of each group. RESULTS: SEM disclosed the eyes of Group A had complete PVD (8/, Group B partial PVD (7/, and Group C (8/ and all the control eyes (24/24) no PVD after 7 days. Partial PVD was found in 4/4 at 0.5 hour and complete PVD was seen in 3/4 at 1 hour in Group A. Immunohistochemistry showed that the amounts of laminin and fibronectin in the vitreoretinal interface were decreased in Group A and B versus the control eyes (P <0.001), but not in Group C versus the control eyes (P >0.05). Electroretinography showed no changes in any group (P >0.05). CONCLUSION: Vitreous injection of plasmin + hyaluronidase induced complete PVD with no obvious toxicity. Plasmin induced partial PVD, but hyaluronidase had no effects.
un recentissimo studio (agosto 2005) che conferma l'efficacia delle iniezioni intravitreali di ialuronidasi in pazienti affetti da emorragie vitreali:
1: Am J Ophthalmol. 2005 Aug 25; [Epub ahead of print] Related Articles, Links
Pooled Efficacy Results From Two Multinational Randomized Controlled Clinical Trials of a Single Intravitreous Injection of Highly Purified Ovine Hyaluronidase (Vitrase((R))) for the Management of Vitreous Hemorrhage.
Kuppermann BD, Thomas EL, de Smet MD, Grillone LR; Vitrase for Vitreous Hemorrhage Study Groups.
Department of Ophthalmology, University of California, Irvine, Irvine, California.
PURPOSE: To evaluate the efficacy of intravitreous ovine hyaluronidase for the management of vitreous hemorrhage. DESIGN: Two prospective, randomized, placebo-controlled, double-masked studies. Safety data are presented in a companion article in the journal. METHODS: Eligible patients with vitreous hemorrhage >/=1 month duration; severe at entry with best corrected visual acuity (BCVA) worse than 20/200 were randomized to 55 IU or 75 IU ovine hyaluronidase or saline. Primary efficacy (clearance of hemorrhage sufficient to see the underlying pathology and completion of treatment when indicated) was measured at months 1, 2, and 3. Key secondary endpoints were: >/=3-line improvement in BCVA; hemorrhage density reduction; and therapeutic utility assessment. RESULTS: The intent-to-treat population for common dose groups (55 IU, 75 IU, saline) consisted of 1125 patients. At baseline, 76.3% had diabetes, 90.4% were not able to read any letters on the eye chart, and mean hemorrhage duration was 120 days. Statistical significance was reached in the 55 IU dose group by months 1 and 2 for the primary efficacy endpoint based on an adjusted P-value. By months 1, 2, and 3, 13.2%, 25.5%, and 32.9% of patients (55 IU) reached primary efficacy compared with 5.5%, 16.2%, and 25.6% of saline-treated patients (P < .001; P = .002; P = .025, respectively). Key secondary endpoints confirmed the treatment effect at both doses and all timepoints (P </= .01). CONCLUSIONS: Fifty-five IU ovine hyaluronidase showed statistically significant efficacy as early as months 1 and 2. These results were supported by outcomes for three key secondary endpoints. These results suggest a therapeutic utility of ovine hyaluronidase in the management of vitreous hemorrhage.
PMID: 16125661 [PubMed - as supplied by publisher]
a proposito degli effetti della ialuronidasi sul gel vitreale, ecco uno studio del famoso prof. bishop di manchester. esso ha dimostrato che questo enzima non conduce alla distruzione o alla liquefazione del gel che compone il vitreo, ma contribuisce in modo determinante alla depolimerizzazione dell'acido ialuronico.
1: Invest Ophthalmol Vis Sci. 1999 Sep;40(10):2173-8. Related Articles, Links
Effects of hyaluronan lyase, hyaluronidase, and chondroitin ABC lyase on mammalian vitreous gel.
Bishop PN, McLeod D, Reardon A.
Department of Ophthalmology and Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, England, UK. firstname.lastname@example.org
PURPOSE: To determine the effects of enzymes on mammalian vitreous gel and to thus infer the structural roles of hyaluronan and chondroitin sulfate in the gel. METHODS: The wet weights of bovine vitreous gels were compared before and after incubation with Streptomyces hyaluronan lyase, chondroitin ABC lyase, testicular hyaluronidase, or buffer alone. The extent of hyaluronan depolymerization was determined by chromatography and that of chondroitin sulfate depolymerization by western blot analysis. RESULTS: After digestion with Streptomyces hyaluronan lyase (30 U/gel), the gel wet weight was the same as that of controls (incubated with buffer alone) despite 94% of the hyaluronan having been depolymerized; when digested with 100 U/gel, the gel wet weight decreased (to 57% of original wet weight versus 86% for controls, P = < 0.001) and hyaluronan was completely depolymerized. Chondroitin ABC lyase digestion (0.2 U/gel) resulted in a slight reduction in gel wet weight (90% versus 96%, P = < 0.001) and depolymerization of 88% of the hyaluronan; the presence of fully digested chondroitin sulfate chains was established. Digestions with 100 and 500 U/gel of testicular hyaluronidase resulted in a decrease (P = < 0.001, both cases) in gel wet weight (53% versus 82%, 100 U/gel; 57%, versus 86%, 500 U/gel) with 75% and 97% hyaluronan depolymerization, respectively. CONCLUSIONS: Depolymerization of all vitreous hyaluronan and of chondroitin sulfate resulted in gel wet weight reduction but not gel destruction. Digestion with 30 U/gel of Streptomyces hyaluronan lyase revealed a small pool (6%) of relatively enzyme-resistant hyaluronan that specifically contributed toward maintaining gel wet weight.
allora è sangue o degenerazione del collagene ecc. le cose mi parte sono estremamente diverse. Torno a chiedere dov'è scritto in quel popò di testo che l'enzima è valido anche per i floaters????????????????????
Effects of vitreous liquefaction on the intravitreal distribution of sodium fluorescein, fluorescein dextran and fluorescent microparticles
Lay Ean Tan1, Werhner Orilla2, Patrick M Hughes3, Susan Tsai4, James A Burke5 and Clive G Wilson6
+ Author Affiliations
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclye, Glasgow, United Kingdom
2Biological Sciences, Allergan Inc., Irvine, United States
3Formulation Sciences, Allergan, Irvine, United States
4Biological Sciences, Allergan Inc., Irvine, United States
5Biological Sciences, Allergan Inc., Irvine, United States
6Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
Correspondence: Lay Ean Tan, Email: email@example.com
Purpose: The effects of vitreous liquefaction in the elderly on the distribution of drugs from intravitreal injections, depots or devices remains unclear. The aim of the present study was to develop a liquefied vitreous model that simulates the aged condition, allowing the study of clinically relevant drug distribution.
Methods: Dutch-belted rabbits were used to develop a study model using hyaluronidase as a vitreolytic agent. The effects of experimental vitreous liquefaction were investigated on intravitreal sodium fluorescein, fluorescein isothiocyanate-dextran (MW= 150kDa) and a suspension of 1µm fluorescent particles. The distribution of these model compounds was monitored using Heidelberg Retinal Angiography (HRA) confocal laser scanning system and ocular fluorophotometer.
Results: Hyaluronidase-treated vitreous humor (n=6) was found to decrease the gel phase to 41 ± 9% (w/w; mean ± SD) as compared to 81 ± 9% in the control eyes (n= (p<0.05). The distribution of sodium fluorescein and fluorescein isothiocyanate dextran was greater in the liquefied vitreous than control. In comparison to the normal vitreous, fluorescent particles sedimented faster in the liquefied vitreous and the distribution was more dispersed and scattered.
Conclusions: A model of vitreous liquefaction in rabbits was successfully generated using intravitreal hyaluronidase. Small and large fluorescent molecules as well as particulates distributed faster in liquefied vitreous as compared to control. This suggests enhanced convective flow, and subsequent faster clearance in liquefied vitreous.
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