Role of cryptochromes in retinal responses to light

Thesis

Cryptochromes 1 and 2 (CRY1-2) are key components of the negative limb of the mammalian circadian clock. Like in many peripheral tissues, Cry1 and Cry2 are expressed in the retina where they are thought to play a role in regulating retinal circadian physiology.

This thesis investigates the role of Cryptochromes in the mammalian retina. The localization and expression pattern of CRY1 and CRY2 in the mouse retina are described, showing that CRY1 is expressed throughout, whereas CRY2 expression is restricted to the outer retina.

Furthermore, circadian rhythms in retinal physiology, including the photopic electroretinogram (ERG) b-wave amplitude, contrast sensitivity and the pupillary light response (PLR) are found to be all attenuated or abolished in CRY1-deficient mice. By contrast, these physiological rhythms are unaffected in mice lacking CRY2, and only photopic ERG rhythms are affected. As such, both CRY1 and CRY2 play roles in regulating normal retinal circadian rhythms, though CRY1 plays a dominant role.

The role of melanopsin in retinal rhythms is also investigated. It is found that loss of melanopsin affects contrast sensitivity rhythms but not PLR rhythms. The work in this thesis suggests that the retinal circadian clock is composed of at least two independent networks of oscillators in the retina which regulate key aspects of retinal physiology.

Lastly, this thesis investigates whether the retinal clock has any downstream effects on the SCN master pacemaker. The experimental results presented here suggest that the retinal clock is capable of rhythmically gating light input to the SCN clock, acting as a zeitnehmer.

Authors: Wong, J

• DOI: 10.5287/ora-kz4bbna7k
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Cry1; magnetoreception; magnetoreceptor; Cry2; Cryptochrome; retinal clock; retinal rhythms; zeitnehmer
• Subjects: Electroretinography; Pupillometry; Cryptochrome; Magnetoreception; Retina; Circadian rhythms; Magnetoreceptors; Contrast sensitivity (Vision); Biological rhythms