Abstract
Retinitis pigmentosa (RP) is an inherited ocular disorder with no effective treatment. RP onset and progression trigger a cascade of retinal disorders that lead to the death of photoreceptors. After photoreceptors death, neuronal, glial and vascular remodeling can be observed in the retina. The purpose of this study was to study if thioredoxin (TRX) administration is able to decrease photoreceptor death in an animal model of RP (rd1 mouse), but also if it is able to modulate the retinal oxidative stress, glial and vascular changes that can be observed as the disease progresses. Wild type and rd1 mice received several doses of TRX. After treatment, animals were euthanized at postnatals days 11, 17, or 28. Glutathione (GSH) and other thiol compounds were determined by high performance liquid chromatography (HPLC). Glial fibrilary acidic protein (GFAP) and anti-ionized calcium binding adaptor molecule 1 (Iba1) were studied by immunohistochemistry. Vascular endothelial growth factor (VEGF) and hepatic growth factor (HGF) expression were determined by western blot. TRX administration significantly diminished cell death in rd1 mouse retinas and increased GSH retinal concentrations at postnatal day 11 (PN11). TRX was also able to reverse glial alterations at PN11 and PN17. No alterations were observed in retinal VEGF and HGF expression in rd1 mice. In conclusion, TRX treatment decreases photoreceptor death in the first stages of RP and this protective effect may be due in part to the GSH system activation and to a partially decrease in inflammation.
Highlights
The name retinitis pigmentosa (RP) describes a heterogeneous group of degenerative and inherited ocular disorders that causes severe visual impairment (Wright et al, 2010; Daiger et al, 2013) and in many cases leads to total blindness
The Thioredoxin and Retinitis Pigmentosa mechanisms of photoreceptors death are not completely clear, three phases can be distinguished in the Retinitis pigmentosa (RP) degeneration process (Jones and Marc, 2005): i) phase I: photoreceptors suffer a period of stress, shortening of rods and a disorganization of their synaptic contacts is observed; ii) phase II: death of photoreceptors takes place, Müller cells form glial fibrotic walls throughout the retina and death of other retinal neurons can occur; iii) phase III: neuronal, glial and vascular remodeling of the retina occurs (Jones et al, 2016)
We studied if TRX was able to decrease photoreceptor death and to modulate the retinal oxidative stress, and glial and vascular changes that can be observed as the disease progress
Summary
The name retinitis pigmentosa (RP) describes a heterogeneous group of degenerative and inherited ocular disorders that causes severe visual impairment (Wright et al, 2010; Daiger et al, 2013) and in many cases leads to total blindness. The Thioredoxin and Retinitis Pigmentosa mechanisms of photoreceptors death are not completely clear, three phases can be distinguished in the RP degeneration process (Jones and Marc, 2005): i) phase I: photoreceptors suffer a period of stress, shortening of rods and a disorganization of their synaptic contacts is observed; ii) phase II: death of photoreceptors takes place, Müller cells form glial fibrotic walls throughout the retina and death of other retinal neurons can occur; iii) phase III: neuronal, glial and vascular remodeling of the retina occurs (Jones et al, 2016) In this last stage of the disease, neural cells dye progressively, and Müller cells fill in the spaces left by them. Hepatic growth factor (HGF) plays a role in ocular angiogenesis and neuroprotection of retinal neurons (Bussolino et al, 1992; Salom et al, 2010; Karamali et al, 2019; Lorenc et al, 2020), it is still unknown whether alterations of this growth factor may be relevant in RP or not
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