The Schlager mouse as a model of altered retinal phenotype

Hypertension is a risk factor for a large number of vision-threatening eye disorders.In this study,we investigated for the first time the retinal neural structure of the hypertensive BPH/2J mouse(Schlager mouse)and compared it to its control counterpart,the normotensive BPN/3J strain.The BPH/2J mouse is a selectively inbred mouse strain that develops chronic hypertension due to elevated sympathetic nervous system activity.When compared to the BPN/3J strain,the hypertensive BPH/2J mice showed a complete loss of outer layers of the neural retina at 21 weeks of age,which was indicative of a severe vision-threatening disease potentially caused by hypertension.To elucidate whether the retinal neural phenotype in the BPH/2J strain was attributed to increased BP,we investigated the neural retina of both BPN/3J and BPH/2J mice at 4 weeks of age.Our preliminary results showed for the first time that the BPH/2J strain develops severe retinal neural damage at a young age.Our findings suggest that the retinal phenotype in the BPH/2J mouse is possibly due to elevated blood pressure and may be contributed by an early onset spontaneous mutation which is yet to be identified or a congenital defect occurring in this strain.Further characterization of the BPH/2J mouse strain is likely to i)elucidate gene defects underlying retinal disease;ii)understand mechanisms leading to neural retinal disease and iii)permit testing of molecules for translational research to interfere with the progression of retinal disease.The animal experiments were performed with the approval of the Royal Perth Hospital Animal Ethics Committee(R535/17-18)on June 1,2017.

Sympathetic stimulation with norepinephrine may come at a cost

Norepinephrine(NE;also known as noradrenaline)is the body’s primary adrenergic neurotransmitter which belongs to the catecholamine family.Norepinephrine has pharmacologic effects on theα1(Suita et al.,2015),α2(Schwartz,1997),β1,β2 andβ3(Tsukada et al.,2003)adrenoceptors.In the brain,norepinephrine increases arousal and alertness,promotes vigilance,enhances formation and retrieval of memory,and focuses attention.It also increases restlessness and anxiety.In the remainder of the body,norepinephrine increases heart rate and blood pressure,triggers the release of glucose from energy stores,increases blood flow to skeletal muscle and increases muscle contraction,reduces blood flow to the gastrointestinal system and its motility and lastly,inhibits voiding of the bladder(Goldstein,2010).This last point is particularly interesting in the context of this perspective piece.