Oxygen-induced retinopathy in the newborn rat: effects of hyperbarism and topical administration of timolol maleate

Ricci, Beatrice; Minicucci, Giuseppe; Manfredi, Alessandra; Santo, Alessandro

doi:10.1007/bf00183596

Cited by 17 publications

(7 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FITC dextran has been used to map the angiogenesis in OIR model in the retinal flat mounts. While adopting the similar procedure, the present study has also observed an avascularised junction between the mid zone of retina and the ora serrata along with microaneurysm which are similar to the findings of others [18, 19, 20]. In order to compare the effect of RRAS blockade with control, this study opted for ERG and retinal vascular tortousity as quantifiable parameters.…”

Section: Discussionsupporting

confidence: 86%

Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention

et al. 2016

View full text Add to dashboard Cite

ObjectiveExamining the Retinal Renin Angiotensin System (RRAS) in the ROP neonates and analyzing the possibility of modulating the RRAS to prevent the progression in Oxygen Induced Retinopathy (OIR) model.MethodVitreous of ROP patients (n = 44, median age 5.5 months) was quantified for RRAS components, VEGF, HIF-1α and compared with age matched control. The involvement of RRAS in ROP was tested in the rat model of OIR and compared with normoxia. Expressions of RAS components, VEGF and HIF-1α in retina were analyzed using qPCR and retinal structure and function was also analyzed. Effect of Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) was evaluated and compared with Bevacizumab which served as a positive control. Drug penetration into retina was confirmed by liquid chromatography coupled ESI-tandem mass spectroscopy (LC-MS/MS).ResultsMultifold increase in the expression of RAS components in human vitreous and rat retina showed their involvement in ROP. ERG & fundus studies in OIR revealed the altered function of retina and were successfully prevented by ARB (telmisartan), ACEI (lisinopril) and bevacizumab. Retinal analysis revealed the presence of ACEI and ARB in their therapeutic levels.ConclusionThis study for the first time demonstrates the upregulated level of RAS components in human ROP vitreous and further that the pharmacological intervention in RRAS can functionally and structurally preserve retina against the progression of ROP in the OIR model.

show abstract

Section: Discussionsupporting

confidence: 86%

Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention

et al. 2016

View full text Add to dashboard Cite

show abstract

“…51 In vivo, oxygen induced rethinopathy in newborn rats was inhibited by timolol treatment. 52 Timolol also displays protective effects against the neuronal damage induced by glutamate in rat retina, 40 further confirming the antioxidant attitude of timolol because glutamate exerts its cytotoxicity through oxidative damage, as demonstrated in retinal ganglion cells. 53 The MTT test used under our experimental conditions specifically evaluates mitochondrial function.…”

Section: Discussionmentioning

confidence: 68%

Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

Izzotti

Saccà²,

Marco

et al. 2007

Eye

View full text Add to dashboard Cite

Purpose A growing evidence in the scientific literature suggests that oxidative damage plays a pathogenic role in primary open-angle glaucoma. Therefore, it is of interest to test whether drugs effective against glaucoma display antioxidant activity. We test the hypothesis that the classic b-blocker therapy for glaucoma with timolol involves the activation of antioxidant protective mechanisms towards endothelial cells. Methods Oxidative stress was induced in cultured human endothelial cells by iron/ ascorbate with or without timolol pretreatment. Analysed parameters included cell viability (neutral red uptake and tetrazolium salt tests), lipid peroxidation (thiobarbituric reactive substances), and occurrence of molecular oxidative damage to DNA (8-hydroxy-2 0 -deoxyguanosine).Results Oxidative stress decreased 1.8-fold cell viability, increased 3.0-fold lipid peroxidation and 64-fold oxidative damage to DNA. In the presence of timolol, oxidative stress did not modify cell viability, whereas lipid peroxidation was increased 1.3-fold, and DNA oxidative damage 3.6-fold only.Conclusions The obtained results indicate that timolol exerts a direct antioxidant activity protecting human endothelial cells from oxidative stress. These cells employ mechanisms similar to those observed in the vascular endothelium. It is hypothesized that this antioxidant activity is involved in the therapeutic effect of this drug against glaucoma.

show abstract

“…Their peripheral retina was avascular, suggesting that the retinal vascular growth had been retarded. As size of avascular area is correlated with disease severity, this avascular zone is likely to be significant (24,25). The central capillary density in this group was higher than controls and showed smaller capillary-free zones around the larger vessels.…”

Section: Discussionmentioning

confidence: 76%

Hypoxic Oxygen Fluctuations Produce Less Severe Retinopathy than Hyperoxic Fluctuations in a Rat Model of Retinopathy of Prematurity

et al. 2004

View full text Add to dashboard Cite

The aim of this study was to investigate whether the mean around which arterial oxygen fluctuations take place was important in a unique animal model of oxygen-induced retinopathy. Retinopathy of prematurity (ROP) is associated with fluctuating arterial oxygen. A recent retrospective study suggested that management of high-risk preterm infants at lower oxygen saturations was associated with less severe ROP. Rat pups were raised in a variable oxygen environment around a high (24%), normal (21%) or low (17%) mean inspired oxygen for 14 d. Rat pups raised in the high (24%) mean variable oxygen environment had more retarded retinal vascular development than did rats raised in an environment that fluctuated around 21% mean oxygen. In contrast, rats raised in a lower mean (17%) but still variable oxygen environment had no discernible retinal differences from controls raised in constant room air. Rats raised in a relatively hypoxic but variable oxygen environment develop less severe retinal vascular abnormalities than those raised in variable oxygen around higher oxygen means. Abbreviations C, group raised in room air DAB, diaminobenzidine Hi, variable oxygen profile around 24% oxygen mean IQR, interquartile range Lo, variable oxygen profile around 17% oxygen mean N, variable oxygen profile around 21% oxygen mean PFA, paraformaldehyde ROP, retinopathy of prematurity TBS, Tris-buffered saline VEGF, vascular endothelial growth factor ROP is a leading cause of blindness among infants in developed (1) and middle-income countries (2). The role of high concentrations of supplemental oxygen was first recognized in the 1950s (3), and subsequent animal studies (4 -6) delineated the pathophysiology. Restrictions on oxygen use led to a reduction in the disease, but the technological advances in the 1970s and 1980s led to infants up to 16 wk preterm surviving. Even with strict oxygen control to prevent hyperoxia the disease incidence began to increase again. The cause of the current disease is generally considered multifactorial (7), however variations in oxygen have been shown important to the development of disease in humans (8, 9) and in animal models (10 -12).Current oxygen therapy for preterm neonates in our neonatal unit (Edinburgh, UK) provides a "safe" transcutaneous range of 6 -10 kPa (45-75 mm Hg). This is considered to minimize hyperoxia-associated ROP and to limit neurologic and pulmonary morbidity from associated hypoxia. However, there are few data to indicate whether these limits are appropriate. In "healthy" preterm infants (without lung disease) of 29 -34 wk gestation, Mok et al. (13) demonstrated a mean (range) of 9 kPa (4.7-10.9 kPa) [67.5 (35-82) mm Hg] over the first few months of life. However, no data are available for the gestations at risk for ROP currently (infants Ͻ 29 wk gestation).A recent retrospective case review suggested that babies Ͻ28 wk gestational age nursed in an oxygen saturation range of 70 -90% had a lower incidence of ROP (14) ABSTRACT107 dence of cerebral palsy or adverse pulmonary out...

show abstract

Oxygen-induced retinopathy in the newborn rat: effects of hyperbarism and topical administration of timolol maleate

Cited by 17 publications

References 9 publications

Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention

Involvement of Renin-Angiotensin System in Retinopathy of Prematurity - A Possible Target for Therapeutic Intervention

Antioxidant activity of timolol on endothelial cells and its relevance for glaucoma course

Hypoxic Oxygen Fluctuations Produce Less Severe Retinopathy than Hyperoxic Fluctuations in a Rat Model of Retinopathy of Prematurity

Contact Info

Product

Resources

About