Biology 2021, 10, 1003. https://doi.org/10.3390/biology10101003 www.mdpi.com/journal/biology Article Characterizations of Hamster Retina as a Model for Studies of Retinal Cholesterol Homeostasis Nicole El-Darzi 1 , Natalia Mast 1 , Brian Dailey 1 , John Denker 1 , Yong Li 1 , Joseph Vance 2 and Irina A. Pikuleva 1, * 1 Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, OH 44106, USA; nae20@case.edu (N.E.-D.); nvm2@case.edu (N.M.); bxd238@case.edu (B.D.); jad6@case.edu (J.D.); yxl665@case.edu (Y.L.) 2 Spective LLC, Durham, NC 27705, USA; jvance@thespectivegroup.com * Correspondence: iap8@case.edu Simple Summary: This work represents a comprehensive evaluation of hamster retina by state-of- the-art methodologies and provides evidence that hamsters may represent a better model for studies of retinal cholesterol maintenance than mice. The latter is an important finding, as disturbances in retinal cholesterol homeostasis are linked to age-related macular degeneration and diabetic reti- nopathy, which are blinding diseases. Abstract: Cholesterol homeostasis in the retina, a sensory organ in the back of the eye, has been studied in mice but not hamsters, despite the latter being more similar to humans than mice with respect to their whole-body cholesterol maintenance. The goal of this study was to begin to assess hamster retina and conduct initial interspecies comparisons. First, young (3-month old) and mature (6-month old) Syrian (golden) hamsters were compared with 3- and 6-month old mice for ocular biometrics and retinal appearance on optical coherence tomography and fluorescein angiography. Of the 30 evaluated hamsters, seven had retinal structural abnormalities and all had increased per- meability of retinal blood vessels. However, hamsters did not carry the mutations causing retinal degenerations 1 and 8, had normal blood glucose levels, and only slightly elevated hemoglobin A1c content. Cholesterol and six other sterols were quantified in hamster retina and compared with sterol profiles in mouse and human retina. These comparisons suggested that cholesterol turnover is much higher in younger than mature hamster retina, and that mature hamster and human retinas share similarities in the ratios of cholesterol metabolites to cholesterol. This study supports further investigations of cholesterol maintenance in hamster retina. Keywords: hamster; retina; cholesterol; retinal abnormalities; retinal blood vessels; diabetes; diabetic retinopathy 1. Introduction Among rodents, mice and rats are perhaps the most common laboratory animals due to their small size, rapid breeding, low maintenance cost, and ease of genetic manipula- tions. Hamsters are a less utilized model, even though they are also small and belong to the same Rodentia order as mice and rats. Hamsters diverged from mice and rats at the family level and represent the rodent family Cricetidae, whereas mice are from the Muridae family [1]. There are 19 species in the Cricetidae family, with the most used laboratory models being Syrian (golden) hamsters (Mesocricetus auratus), Chinese (dwarf) hamsters (Cricetulus griseus), and Djungarian (or Siberian) hamsters (Phodopus sungorus) [1]. Yet none of these models have been characterized for cholesterol homeostasis in the retina, a sensory organ lining the back of the eye. This is in contrast to mice, whose retinal choles- terol maintenance has been intensively studied [2,3] but has not yet been compared to that Citation: El-Darzi, N.; Mast, N.; Dailey, B.; Denker, J.; Li, Y.; Vance, J.; Pikuleva, I.A. Characterizations of Hamster Retina as a Model for Studies of Retinal Cholesterol Homeostasis. Biology 2021, 10, 1003. https://doi.org/ 10.3390/biology10101003 Academic Editor: Raju V. S. Rajala Received: 14 September 2021 Accepted: 4 October 2021 Published: 6 October 2021 Publisher’s Note: MDPI stays neu- tral with regard to jurisdictional claims in published maps and institu- tional affiliations. Copyright: © 2021 by the authors. Li- censee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and con- ditions of the Creative Commons At- tribution (CC BY) license (http://crea- tivecommons.org/licenses/by/4.0/).