Niggemann, Birgit, Atorf, Jenny, Fridrichs-Gromoll, Stephanie, Korte, Sven, Kremers, Jan, Mecklenburg, Lars, Wiederhold, Andreas, Hill, Marilyn, Pilling, Andrew and Mansfield, Keith (2017) Feasibility of intravitreal injections and ophthalmic safety assessment in marmoset (Callithrix jacchus) monkeys. Primate Biology, 4, 93- (4-93-2). pp. 93-100.

Abstract

Feasibility of intravitreal injections and ophthalmic safety assessment in marmoset (Callithrix jacchus) monkeys

Birgit Niggemann1), Sven Korte1), Marilyn Hill3), Jacintha Shenton3), Andrew Pilling3), Lars Mecklenburg1), Stephanie Fridrichs-Gromoll1), Andreas Wiederhold1), Jenny Atorf2),), Jan Kremers2)
1) Covance Laboratories GmbH, Muenster, Germany
2) Department of Ophthalmology, University Hospital Erlangen, Erlangen, Germany
3) Novartis Pharma AG, CH-4002 Basel, Switzerland

To support clinical trials of new drugs to be given by the intravitreal route for the treatment of ocular diseases, assessment of the safety of administration of the investigational drug by the intravitreal route to a laboratory species is a regulatory requirement. Due to the high similarity of ocular morphology and physiology between humans and nonhuman primates (NHPs) and the species-specificity of many biotherapeutics, the monkey often is a necessary model. To this end, intravitreal administration procedures and assessments of ocular toxicity in cynomolgus monkeys (Macaca fascicularis) are well-established. In contrast, the common marmoset monkey (Callithrix jacchus) is not a standard model for ocular toxicity studies due to its general sensitivity to laboratory investigations and small size of the eye. However, apart from a polymorphism in red-green color vision, no or only minor structural and functional differences in the retina of marmosets were described in comparison to macaques. In addition, recordings from single neurons in the lateral geniculate nucleus showed that the functional properties of visually responsive cells in marmosets are very similar to those in the macaque. Thus, the marmoset is a potentially interesting alternative NHP model if the macaque is not the relevant species. It was the purpose of the present work to study whether the marmoset is a useful alternative to the cynomolgus monkey that can be used in toxicological studies. Six marmoset monkeys (n=6) received repeated (every 2 weeks for a total of 4 doses) intravitreal injections of 10 or 20 µL of a placebo. The animals were assessed using measurements of intraocular pressure, standard ophthalmological investigations, and full-field electroretinography (ERG). At the end of the dosing period, the animals were sacrificed and the retina was assessed histologically. ERG assessment revealed similar results when comparing pre-dose to end of study data, and there was no difference between the two dose volumes. A transient increase in the intraocular pressure was seen immediately after dosing which was more pronounced after dosing of 20 µL compared to 10 µL. It is concluded that based on ophthalmologic and microscopic observations, 10 µl as well as 20 µl intravitreal injection of a placebo are well tolerated in the marmoset. We conclude that the common marmoset is an interesting alternative to the cynomolgus monkey for ocular toxicity testing.

Item Type:	Article
Keywords:	Intravitreal, Marmoset monkeys
Date Deposited:	27 May 2017 00:45
Last Modified:	27 May 2017 00:45
URI:	https://oak.novartis.com/id/eprint/31067