Understanding Cone Photoreceptor Cell Death in Achromatopsia

Abstract

Colour vision is only achieved in the presence of healthy and functional cone photoreceptors found in the retina. It is an essential component of human vision and usually the first complaint patients undergoing vision degeneration have is the loss of daylight colour vision. Therefore, an understanding of the biology and basic mechanisms behind cone death under the degenerative state of retinal dystrophies and how the activation of the apoptotic pathway is triggered will provide valuable knowledge. It will also have broader applications for a spectrum of visual disorders and will be critical for future advances in translational research.

Primary and Secondary Cone Cell Death Mechanisms in Inherited Retinal Diseases and Potential Treatment Options

“…Interestingly, cones are remarkably sensitive to degeneration in IRD. Their degeneration can occur either directly via mutations in cone-specific genes (primary cone death), as seen in conditions such as achromatopsia or cone dystrophies, or indirectly as in conditions such as retinitis pigmentosa, where a primary degeneration of rods is followed by a secondary degeneration of cones (secondary cone death) [ 9 , 10 ]. Congenital achromatopsia, or total colour blindness, is a rare autosomal recessive cone-dystrophy affecting 1:30,000 people worldwide [ 1 , 11 ].…”

CNGB3 mutations cause severe rod dysfunction

“…In addition, work in mouse models has shown significant correlations between cone cell death and CNG channel abnormalities. A recent review of cone cell death in achromatopsia [36] has outlined several mechanisms that may contribute to cone apoptosis; stress markers associated with the endoplasmic reticulum are increased in CNGA3 -/and CNGA3 -/knockout 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 shown to increase endoplasmic reticulum stress [37].…”

Validating Fluorescent Chrnb4.EGFP Mouse Models for the Study of Cone Photoreceptor Degeneration

“…Several studies into the biology of cones in health and disease have relied on data from animal models of a disorder called achromatopsia, one of the few IRDs that affect cone photoreceptors exclusively. 6 Also referred to as rod monochromacy, achromatopsia is a devastating early onset disease estimated to affect 1:30,000 to 1:50,000 people worldwide. 7 Clinical symptoms start at birth/early infancy and include not only completely absent color discrimination with no recordable electroretinogram cone function, but also congenital pendular nystagmus, poor visual acuity, severe photophobia, and hemeralopia.…”