Hypoxic–ischemic retinal injury in rat pups

Abstract

Background: Visual loss associated with brain damage, especially hypoxic-ischemic (hI) encephalopathy, is the most common cause of visual impairment in children in developed countries. We hypothesized that hI insults can cause long-term damage in immature eyes. Methods: In postnatal day 7 rat pups, hI was induced by unilateral common carotid artery ligation followed by hypoxia. Retina damage was assessed by electroretinography (eRG) and cell counting. Neuronal injury and astrogliosis were evaluated by terminal deoxynucleotidyl transferase nick-end labeling, cleaved caspase 3, eD1, and glial fibrillary acidic protein immunostaining. results: We observed rapid and persistently extensive injuries in the ganglia cell layer (GcL), inner plexiform layer, and inner nuclear layer (INL) in ipsilateral retinas after hI injury, corresponding to the marked alteration in eRG. hI insult caused prominent microglial and Műller cell activation in ipsilateral inner retinas. Neuronal death in the GcL and INL after hI injury was mainly apoptotic, involving caspase-dependent pathways. conclusion: Our study demonstrated the first evidence of hI retinal damage at both the pathological and functional level using the Vannucci model in neonatal rats. Because retinal damage is often associated with hI injury, it is important to demonstrate that a particular neuroprotective strategy effectively preserves the retina in addition to the brain.

Systemic 7,8-Dihydroxyflavone Treatment Protects Immature Retinas Against Hypoxic-Ischemic Injury via Müller Glia Regeneration and MAPK/ERK Activation

“…The extent of retinal damage was quantified by two independent observers, in two nonoverlapping visual fields (250 3 250 lm) within central areas (100 lm from the optic disc). 8 …”

“…8 Therefore, future therapeutic strategies for treating HI insults should take into account the retina in addition to the brain. Furthermore, it has been shown that BDNF enhances RGC survival and function when injected both to the eyes and central visual pathway than only to the eyes.…”

“…8 The pupils were dilated by 1% Mydriacyl (Alcon, Puurs, Belgium) and 1% Cyclogyl (Alcon, Puurs, Belgium), and the eyes were dark-adapted for 1 hour. After the rats were anesthetized by intramuscular injection of Zoletil 50 (25 mg/ kg; Virbac, Carros, France) and Rompun (10 mg/kg; Bayer Korea, Seoul, Korea), the recording electrode was placed on the cornea with 0.5% methyl cellulose (Omni Vision, Zürich, Switzerland).…”

“…The animals were then placed in airtight 500-mL containers partially submerged in a 378C water bath, through which humidified 3 L/min 8% oxygen (balance, nitrogen) was maintained for 2 hours. 8 After completion of the procedure, the pups were placed back in their cages. Pups that did not receive the vessel occlusion and hypoxic injury were considered as sham controls.…”

“…4 However, we have previously demonstrated that HI insult can also cause significant histologic and functional damages to the immature retina, including hypoxic stress, apoptosis, and neuroinflammation. 8,9 Therefore, it is important to implement a neuroprotective strategy that is beneficial for both the retina and the brain.…”