Neonatal and Juvenile Ocular Development in Göttingen Minipigs and Domestic Pigs: A Histomorphological and Immunohistochemical Study

Abstract

Pigs are considered one of the relevant animal models for ocular research as they share several histological and anatomical similarities with the human eye. With the increasing interest in juvenile animal models, this study aimed to describe the postnatal development of ocular structures in 16 Göttingen minipigs and 25 F2 domestic pigs, between birth and 6 months of age, using histopathology and immunohistochemistry against Ki-67, caspase-3, calbindin, glial fibrillary acidic protein, rhodopsin, and synaptophysin. All ocular structures in both pig breeds were incompletely developed at birth and for variable periods postnatally. Noteworthy histological features of immaturity included vascularization in the corneal stroma in neonatal Göttingen minipigs, increased cellularity in different substructures, remnants of the hyaloid vasculature, short and poorly ramified ciliary body processes, and a poorly developed cone inner segment. Increased cellular proliferation, highlighted by abundant Ki-67 immunolabeling, was observed in almost all developing structures of the pig eye for variable periods postnatally. Apoptosis, highlighted with caspase-3 immunolabeling, was observed in the retinal inner nuclear layer at birth and in the regressing hyaloid vasculature remnants. Immunohistochemistry against rhodopsin, synaptophysin, and calbindin demonstrated the short size of the developing photoreceptors and the immature cone inner segment morphology. Calbindin labeling revealed significant differences in the amount of positively labeled cone nuclei between the retinal area centralis and the non–area centralis regions. The elongation of Müller cell processes in the developing retina was shown with glial fibrillary acidic protein. In both pig breeds, the eyes reached histomorphological and immunohistochemical maturity at 6 months of age.

Laser-Induced Porcine Model of Experimental Retinal Vein Occlusion: An Optimized Reproducible Approach

“…The visual streak is horizontally oriented and located superior to the optic nerve head extending to the ora serrata [ 45 , 46 ] Klik eller tryk her for at skrive tekst. The visual streak consists of a relatively stable and high concentration of cone photoreceptors compared with other retinal regions [ 45 , 47 ]. Therefore, the porcine retina allows for studies of experimental RVO in a cone-rich area if the visual streak is affected by the induced occlusion.…”

Scientific and Regulatory Policy Committee Points to Consider: Fixation, Trimming, and Sectioning of Nonrodent Eyes and Ocular Tissues for Examination in Ocular and General Toxicity Studies

“…16,27 However, the visual streak of minipigs is not characterized by the focal retinal thickening/bulge that defines the area centralis as observed in dogs. Although the visual streak has been incorrectly referred to as the area centralis in some publications regarding the pig retina, 13,32- 34 the region of high ganglion cell density in this species should be designated as the visual streak, and area centralis terminology should not be used in microscopic evaluation of minipig eyes.…”

The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development

“…Continuous efforts are being made to better characterize the (juvenile) pig in the fields of ophthalmology [ 251 , 252 ], neurodevelopment [ 28 ], immunology [ 28 ], and drug absorption, metabolism and toxicity [ 35 , 43 , 45 , 253 , 254 , 255 , 256 ], although there is still evidence supporting the need for more background information in pigs [ 253 ]. Moreover, differences in between breeds exist [ 257 ] and, since fully characterizing all the pig breeds available is a long-term task, most efforts concentrate in studying the most used pig breed in pharmacological studies in Europe, the Göttingen Minipig [ 35 , 43 , 44 , 45 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 ]. Inter-breed differences are magnified due to the lack of standardization regarding food and feeding patterns, age and sex of pigs used in research [ 275 ].…”