The Intoxication Effects of Methanol and Formic Acid on Rat Retina Function

Abstract

Objective. To explore the potential effects of methanol and its metabolite, formic acid, on rat retina function. Methods. Sprague-Dawley rats were divided into 3- and 7-day groups and a control. Experimental groups were given methanol and the control group were provided saline by gavage. Retinal function of each group was assessed by electroretinogram. Concentrations of methanol and formic acid were detected by GC/HS and HPLC, respectively. Results. The a and b amplitudes of methanol treated groups decreased and latent periods delayed in scotopic and photopic ERG recordings. The summed amplitudes of oscillatory potentials (OPs) of groups B and C decreased and the elapsed time delayed. The amplitudes of OS1, OS3, OS4, and OS5 of group B and OS3, OS4, and OS5 of group C decreased compared with the control group. The IPI1 of group B and IPI1-4 of group C were broader compared with the control group and the IPI1-4 and ET of group B were broader than group C. Conclusions. Both of scotopic and photopic retinal functions were impaired by methanol poisoning, and impairment was more serious in the 7-day than in the 3-day group. OPs, especially later OPs and IPI2, were more sensitive to methanol intoxication than other eletroretinogram subcomponents.

Electrophysiological Studies on The Dynamics of Luminance Adaptation in the Mouse Retina

“…Differences in the adaptation kinetics of the different OP wavelets might imply that they are generated by different inner retinal networks. This was first suggested by Wachtmeister [36], and is further supported by a recent study in rats showing different OP peaks to react differently to methanol intoxication (Liu et al [37]). In regards to the influences of adaptation on sinusoidally-modulated flicker ERG responses, we show, for the mouse, that its first harmonic amplitudes decrease during adaptation to high light levels, whereas they increase during adaption to low light levels.…”

Methanol-induced optic neuropathy: a still-present problem

“…Similarly, the experiment of Chen et al revealed the more pronounced cone damage in the F-ERG recording in rats after a 7 day period of methanol intoxication (Chen et al 2013 ). On the other hand, Liu et al showed no improvement in both scotopic and photopic recordings of ERG in rats performed on the third and seventh day after intoxication (Liu et al 2016 ). In case reports involving human ERG recordings, a and b wave amplitude reduction is typically seen after both acute and chronic methanol exposure (Ingemansson 1984 ; McKellar et al 1997 ; Ruedemann 1962 ), which proves abnormalities in the process of photoreceptor hyperpolarization, as well as depolarization disorders of Muller glial cells with disturbances in transmission between photoreceptors, bipolar cells, and RGCs, respectively (Eells et al 1996 ; McKellar et al 1997 ).…”

“…Importantly, as blood pH decreases, the concentration of non-ionized methanol increases, which determines its increased penetration into tissues and a more extensive range of their damage (Garner et al 1995 ). Moreover, animal studies have shown that despite almost complete metabolism and removal of methanol from the body, the concentration of formic acid simultaneously tends to persist, causing further tissue damage and delayed regeneration of retinal function (Liu et al 2016 ).…”

“…After ingestion, methanol is easily distributed in the body—its presence in the blood, urine, cerebrospinal fluid (CSF), as well as in the vitreous and aqueous humor during a post-mortem examination of poisoned victims was detected (Benton and Calhoun 1953 ). Due to its rapid absorption by the oral mucosa and further parts of the gastrointestinal tract, methanol reaches its maximum concentration in the serum after 30–90 min (Abrishami et al 2011 ; Liu et al 2016 ). Then, methanol undergoes slow liver metabolism to its toxic metabolites: formaldehyde, the intermediate compound with a serum half-life of about 1 min, and the more stable, and toxic formic acid.…”

“…1 ). These reactions are catalyzed by specific enzymes—alcohol dehydrogenase 1b (ADH1b), aldehyde dehydrogenase (ALDH), and N-10-formyltetrahydrofolate dehydrogenase (10-CHO-THF), respectively (González-Quevedo et al 2002 ; Liu et al 2016 ). There are two more specific pathways of exogenous methanol metabolism, the first one involving monooxygenase cytochrome P450 Family 2 Subfamily E Member 1 (CYP2E1), the activity of which is particularly expressed at high methanol concentrations in tissues, while the second pathway involves the enzyme catalase-H 2 O 2 (Dorokhov et al 2015 ).…”