Effects of Bevacizumab (Avastin) on Retinal Cells in Organotypic Culture

Abstract

Bevacizumab was well tolerated by ganglion and photoreceptor cells even at concentrations fivefold higher than those used clinically. The increased expression of SMA is an indication of the loss of functional VEGF modulating smooth muscle cells in mature vessels.

Retinal and Ocular Toxicity in Ocular Application of Drugs and Chemicals – Part II: Retinal Toxicity of Current and New Drugs

“…Their results showed no toxic effects on ganglion or photoreceptor cells at any concentration of bevacizumab. However, they observed significantly enhanced smooth muscle actin expression in retinal blood vessels in the presence of bevacizumab, which may imply a loss of smooth muscle cell modulation in normal retinal vessels by VEGF [86] . In contrast to those data, Luthra et al [83] found no toxicity to microvascular retinal cells in vitro after their exposure to 0.125, 0.25, 0.50 and 1 mg/ml bevacizumab for up to 24 h. A large body of animal studies has been released about the biocompatibility and safety of bevacizumab for ophthalmology.…”

“…In this context, vascular endothelial cells produce and depend on VEGF for their multiple bioactivities, thereby being susceptible to anti-VEGF drugs. To study the effects of bevacizumab on various types of retinal cells, Kaempf et al [86] exposed cultured adult porcine neurosensory retinas joined to the RPE/ choroid layer to 3 doses of bevacizumab (0.25, 0.5 and 1.25 mg/ml) for 3 days. Their results showed no toxic effects on ganglion or photoreceptor cells at any concentration of bevacizumab.…”

Effects of intravitreal bevacizumab (Avastin) on the porcine retina

“…We found also no signs of reactive gliosis or apoptosis after administration of bevacizumab. Whereas VEGF antagonists have already been tested on porcine tissue under in vitro conditions [27,30], this is, to the best of our knowledge, the first study that showed that intravitreal bevacizumab does not alter the structure of the healthy porcine retina in vivo. However, we found distinct alterations in the transcriptional expression of proteins implicated in the development/resolution of edema.…”

“…However, the rabbit retina is non-vascularized (with the exception of the medullary rays), and thus data obtained in rabbit retinas do not necessarily reflect the conditions in vascularized retinas such as the porcine and human retina. Using human and porcine retinal tissue, it has been shown that bevacizumab cross-reacts with the porcine VEGF [27]. Therefore, we tested the effects of a single intravitreal administration of bevacizumab on the integrity of the porcine retina at light and electron microscopic levels, and determined by immunohistochemical and real-time RT-PCR analysis whether or not bevacizumab induces retinal gliosis or apoptosis.…”

Effects of Intravitreal Bevacizumab in Repeated Doses

“…31 However, in a recent cell culture study, bevacizumab was well tolerated by ganglion and photoreceptor cells even at concentrations fivefold higher than those used clinically. 32 The dosage of 1.25 mg (0.05 mL) is the most commonly injected dosage currently. [11][12][13][14][15] Our findings also support the findings of Kaempf et al, 32 validating that injecting a 2.7 times more concentrated dosage of bevacizumab did not cause any histopathologic changes in the rabbit eyes.…”