Abstract

In both humans and dogs, the primary risk factor for glaucoma is high intraocular pressure (IOP), which may be caused by iridocorneal angle (ICA) abnormalities. Oxidative stress has also been implicated in retinal ganglion cell damage associated with glaucoma. A suspected inherited form of glaucoma was recently identified in Eurasier dogs (EDs), a breed for which pedigrees are readily available. Because of difficulties in assessing ICA morphology in dogs with advanced glaucoma, we selected a cohort of apparently healthy dogsfor the investigation of ICA morphological status, IOP and plasma concentrations of oxidative stress biomarkers. We aimed to establish correlations between these factors, to identify predictive markers of glaucoma in this dog breed. A cohort of 28 subjects, volunteered for inclusion by their owners, was selected by veterinary surgeons. These dogs were assigned to four groups: young males, young females (1–3 years old), adult males and adult females (4–8 years old). Ocular examination included ophthalmoscopy, tonometry, gonioscopy, biometry and ultrasound biomicroscopy (UBM), and the evaluation of oxidative stress biomarkers consisting of measurements of plasma glutathione peroxidase (GP) activity and taurine and metabolic precursor (methionine and cysteine) concentrations in plasma. The prevalence of pectinate ligament abnormalities was significantly higher in adult EDs than in young dogs. Moreover, in adult females, high IOP was significantly correlated with a short axial globe length, and a particularly large distance between Schwalbe's line and the anterior lens capsule. GP activity levels were significantly lower in EDs than in a randomized control group of dogs, and plasma taurine concentrations were higher. Hence, ICA abnormalities were associated with weaker antioxidant defenses in EDs, potentially counteracted by higher plasma taurine concentrations. This study suggests that EDs may constitute an appropriate canine model for the development of glaucoma. This cohort will be used as a sentinel for longitudinal monitoring.

Highlights

  • Glaucoma, the second most common cause of blindness worldwide [1], is a group of ophthalmic diseases characterized by the loss of retinal ganglion cells (RGCs) whose function is to transfer visual information to the brain through the optic nerve.High intraocular pressure (IOP) is considered a major risk factor for glaucomatous neuropathies [2]

  • Primary glaucoma has been reported to occur at a high prevalence in various dog breeds which is consistent with the existence of hereditary forms [27] [28] [29] [30]

  • In a cohort of healthy Eurasier dogs (EDs) without a diagnosis of glaucoma, we found that IOP values were towards the upper end of the mean values obtained for dogs with Tonovet [39,40,43], but that these values tend to decrease with age

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Summary

Introduction

The second most common cause of blindness worldwide [1], is a group of ophthalmic diseases characterized by the loss of retinal ganglion cells (RGCs) whose function is to transfer visual information to the brain through the optic nerve.High intraocular pressure (IOP) is considered a major risk factor for glaucomatous neuropathies [2]. A progressive loss of vision can occur in patients with normal tension as well as when their IOP is controlled with drugs [4,5], and oxidative stress is well known to play a critical role in RGC degeneration [6]. This role has been suggested by (i) the decrease in systemic glutathione levels in patients with primary open-angle glaucoma [7] and (ii) the association of this form of glaucoma with a polymorphism of the glutathione S-transferase gene [8]. The importance of combating oxidative stress to ensure RGC survival was confirmed by the prevention of RGC degeneration by taurine, a major antioxidant [9]

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