Reduced severity of oxygen-induced retinopathy in the newborn rat after topical administration of timolol maleate

Ricci, Beatrice; Calogero, Giuseppe; Caprilli, Alessandra; Quaranta‐Leoni, Francesco M.

doi:10.1007/bf00154877

Cited by 7 publications

(8 citation statements)

References 12 publications

(15 reference statements)

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“…The findings from the present study confirm our previous observations [1, 2]that drug-induced reduction of the IOP can diminish the severity of OIR in the newborn rat. Subpalpebral inoculation of timolol maleate diminished the IOP from a control mean of 8.25 ± 0.32 mm Hg to 5.15 ± 0.24 mm Hg without significantly altering the mean arterial pressure.…”

Section: Discussionsupporting

confidence: 82%

“…This procedure, which involves intracardiac injection of India ink, has been described in detail in other publications of ours [1, 10]. After approximately 3 min of perfusion, the ratling’s left eye was removed and the retina isolated.…”

Section: Methodsmentioning

confidence: 99%

“…In the past, we have shown that the severity of OIR in the newborn rat can be reduced by lowering the intraocular pressure (IOP) [1, 2]. To clarify the mechanisms underlying this effect, we conducted an immunohistochemical study aimed at evaluating VEGF protein expression in ratlings exposed to an OIR protocol with and without topical treatment with a nonselective β-adrenergic receptor-blocking agent.…”

Section: Introductionmentioning

confidence: 99%

“…Since 1987, we have been using newborn Wistar rats for studies of this type [1, 2], since the retinal vessel precursors in this model are mesenchymal elements that are similar to the spindle cells of the immature human retina [3]. OIR can be produced in these animals by exposing them to a hyperoxic environment for the first 5 days of life, followed by a 5- to 7-day recovery period in room air.…”

Section: Introductionmentioning

confidence: 99%

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Oxygen-Induced Retinopathy in the Newborn Rat: Morphological and Immunohistological Findings in Animals Treated with Topical Timolol Maleate

Ricci

Maggiano

2000

Ophthalmologica

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Oxygen-induced retinopathy (OIR) similar to that seen in premature infants can be produced in newborn rats by exposure to 80% oxygen for the first 5 days of life, with subsequent recovery for 7 days in a room air environment. Previous studies have shown that the latter phase is associated with degeneration of retinal astrocytes. In the absence of astrocytes, the vascular endothelial growth factor (VEGF) is produced by the neurons of the inner retina. In this study, immunohistochemical methods were used to assess retinal expression of VEGF protein in ratlings exposed to the above protocol, with and without simultaneous treatment with topical timolol maleate. Intraocular pressure (IOP) and arterial pressure were measured. The severity of OIR was also evaluated in retinal flat mounts after India ink perfusion. The mean IOP was 8.25 ± 0.32 mm Hg in untreated ratlings and 5.15 ± 0.24 mm Hg in timolol-treated animals. OIR in retinas from the timolol group was less severe than that seen in untreated ratlings. VEGF protein expression was almost completely absent in the latter group. Retinas from timolol-treated animals expressed VEGF protein, though the level was inferior to that found in controls raised under room air conditions. In conclusion, these data seem to indicate that experimental OIR can be attenuated by a reduction of the IOP during and after oxygen supplementation. It is possible that these effects are due to improved ocular perfusion pressure, which would mitigate the hypoxic insult to the retina during the room air recovery period.

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Section: Discussionsupporting

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxygen-Induced Retinopathy in the Newborn Rat: Morphological and Immunohistological Findings in Animals Treated with Topical Timolol Maleate

Ricci

Maggiano

2000

Ophthalmologica

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“…2007). In contrast, a decrease in VEGF has been observed in the retinas of neonatal OIR rats, in which a reduction in intraocular pressure induced by the β‐AR antagonist timolol diminishes the severity of OIR (Ricci et al. 1991, 1995, 2000).…”

Section: The Role Of β‐Adrenergic Receptors (β‐Ars)mentioning

confidence: 98%

The pathophysiology of retinopathy of prematurity: an update of previous and recent knowledge

Cavallaro

Filippi

Bagnoli

et al. 2013

Acta Ophthalmologica

166

143

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ABSTRACT.Retinopathy of prematurity (ROP) is a disease that can cause blindness in very low birthweight infants. The incidence of ROP is closely correlated with the weight and the gestational age at birth. Despite current therapies, ROP continues to be a highly debilitating disease. Our advancing knowledge of the pathogenesis of ROP has encouraged investigations into new antivasculogenic therapies. The purpose of this article is to review the findings on the pathophysiological mechanisms that contribute to the transition between the first and second phases of ROP and to investigate new potential therapies. Oxygen has been well characterized for the key role that it plays in retinal neoangiogenesis. Low or high levels of pO 2 regulate the normal or abnormal production of hypoxia-inducible factor 1 and vascular endothelial growth factors (VEGF), which are the predominant regulators of retinal angiogenesis. Although low oxygen saturation appears to reduce the risk of severe ROP when carefully controlled within the first few weeks of life, the optimal level of saturation still remains uncertain. IGF-1 and Epo are fundamentally required during both phases of ROP, as alterations in their protein levels can modulate disease progression. Therefore, rhIGF-1 and rhEpo were tested for their abilities to prevent the loss of vasculature during the first phase of ROP, whereas anti-VEGF drugs were tested during the second phase. At present, previous hypotheses concerning ROP should be amended with new pathogenetic theories. Studies on the role of genetic components, nitric oxide, adenosine, apelin and b-adrenergic receptor have revealed new possibilities for the treatment of ROP. The genetic hypothesis that single-nucleotide polymorphisms within the b-ARs play an active role in the pathogenesis of ROP suggests the concept of disease prevention using b-blockers. In conclusion, all factors that can mediate the progression from the avascular to the proliferative phase might have significant implications for the further understanding and treatment of ROP.Key words: erythropoietin -hypoxia-inducible factor 1 -insulin-like growth factor-1 -neovascularization -pathophysiology -placental growth factor -retinopathy of prematurity -vascular endothelial growth factor -b-adrenergic receptors Acta Ophthalmol. 2014: 92: 2-20

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

Ricci

Minicucci

Manfredi

et al. 1995

Graefe's Arch Clin Exp Ophthalmol

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The highly significant protective effects of hyperbarism and timolol observed in this study are not fully understood. We speculate that vasoconstriction induced by the hyperbarism reduces the amount of oxygen that reaches the retina from the choroid during O2 supplementation, while an increased ocular perfusion pressure caused by timolol-induced reduction of the intraocular pressure might decrease the stimulus to vasoproliferation that normally occurs with room-air recovery.

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Reduced severity of oxygen-induced retinopathy in the newborn rat after topical administration of timolol maleate

Cited by 7 publications

References 12 publications

Oxygen-Induced Retinopathy in the Newborn Rat: Morphological and Immunohistological Findings in Animals Treated with Topical Timolol Maleate

Oxygen-Induced Retinopathy in the Newborn Rat: Morphological and Immunohistological Findings in Animals Treated with Topical Timolol Maleate

The pathophysiology of retinopathy of prematurity: an update of previous and recent knowledge

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

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