Taurine deficiency damages photoreceptors and retinal ganglion cells in vigabatrin-treated neonatal rats

Abstract

The anti-epileptic drug Vigabatrin induces an irreversible constriction of the visual field, but is still widely used to treat infantile spasms and some forms of epilepsy. We recently reported that vigabatrin-induced cone damage is due to a taurine deficiency. However, optic atrophy and thus retinal ganglion cell degeneration was also reported in children treated for infantile spasms. We here show in neonatal rats treated from postnatal day 4 to 29 that the vigabatrin treatment triggers not only cone photoreceptor damage, disorganisation of the photoreceptor layer and gliosis but also retinal ganglion cell loss. Furthermore, we demonstrate in these neonatal rats that taurine supplementation partially prevents these retinal lesions and in particular the retinal ganglion cell loss. These results provide the first evidence of retinal ganglion cell neuroprotection by taurine. They further confirm that taurine supplementation should be administered with the vigabatrin treatment for infantile spasms or epilepsy.

Recent Advances in the Pharmacotherapy of Infantile Spasms

“…One study in rodents showed that vigabatrin-associated retinopathy is associated with light exposure [72]. More recently, it has been suggested that a deficiency of taurine is implicated in the pathogenic process of vigabatrinassociated retinopathy [73,74]. A pharmacogenetic exploration of vigabatrin-induced visual field constriction has also been undertaken, although no clear association has been identified [75].…”

“…Limiting light exposure is also a simple and safe recommendation to limit the extent of vigabatrin-induced retinal lesions [74].…”

“…There are some Class IV studies of topiramate [80][81][82], valproic acid [83,84], Class I of sulthiame [85] and Class IV of zonisamide [86][87][88][89], pyridoxine [90,91], nitrazepam [92], levetiracetam [93], lamotrigine [94] and a ketogenic diet [95,96]. Topiramate is a popular second-line treatment of infantile spasms and is often used as first-line treatment, especially where there is no access to vigabatrin [74] (Class IV). There is variable slow or fast titration up to 24 mg/kg/ day [81], and the response is 40 % [80,81].…”

Inner Blood-Retinal Barrier Transporters: Relevance to Diabetic Retinopathy

“…In a study with knockout mice, taut -/-mice exhibited an 80 to 90% reduction in taurine levels in the retina when compared with wild-type mice, showing that TAUT is responsible for the retinal homeostasis of taurine (Warskulat et al, 2007). Diabetic patients exhibit taurine deficiency, and a recent report shows that a reduced level of taurine in the retina causes the loss of cone photoreceptor and retinal ganglion cells, suggesting that retinal taurine deficiency is one of the exacerbating factors for diabetic retinopathy (Franconi et al, 1995;Jammoul et al, 2010). Reports have been published describing that taurine administration reduces the severity of the symptoms of diabetes (Barber, 2003;Moloney et al, 2010;Nakamura et al, 1999).…”

Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA

“…[9][10][11] Taurine may act as a GABA transporter substrate, 12,13 and GABA and taurine transporters may have reciprocal interrelationships. Vigabatrin (VGB)-induced retinotoxicity has been linked to corresponding taurine deficiency, 14,15 of interest because VGB increases CNS GABA. Thus, our rationale for evaluating taurine centered on its successful use in the murine model, potential GABA transporter activity, and antioxidant effects.…”