Vetnuus | Januarie 2024 38 « BACK TO CONTENTS This “Terrible Trio” are commonly seen in veterinary practice and frequently overlooked in the consulting room, which can lead to severe uveitis, glaucoma and potential enucleation of blind eyes. This article aims to clearly outline the mechanism and management of these problems. At about day 17 in the embryological development of the dog’s eye, the surface ectoderm buffs up against the developing optic vesicle and inductive signals from the optic vesicle result in the invagination of the ectoderm into the optic cup forming the lens placode. This initiates the origins of the lens vesicle and future lens. Interestingly, it is the primitive retina that promotes primary lens fibre formation in the adjacent lens epithelial cells. The lens develops with the nucleus occupying most of the lens by volume and, as the animal ages, the lens remains metabolically active with lens epithelial cell division occurring at the equator only. The lens grows throughout life, with newly formed fibres being added continuously to the outermost cortex, causing compression of the central, older zone of lens fibres. This results in a hardening of the central nucleus (i.e., nuclear sclerosis), which reduces accommodation ability as the lens ages. The thickness of the capsule varies by region, with the thinnest being the posterior pole. The canine lens capsule thickness is 8–12 μm at the equator, 50–70 μm anteriorly, and only 2–4 μm posteriorly. Mature lens fibres become dependent on the anterior epithelium for maintaining a critical level of dehydration, which allows the soluble proteins to be functionally effective, and provide a healthy level of reduced glutathione. The alpha, beta and gamma crystalline lens proteins act as inhibitors of apoptosis, and it is only when this homeostatic balance changes that cataract formation occurs. The lens capsule separates the lens proteins from the rest of the globe and body. These sequestered lens proteins within the lens capsule developed before the foetal immune system developed and thus are privileged proteins in the eye. We will see later that this is an important concept in the development of lens-induced uveitis [LIU]. Stage 1: Diabetes: A cataract is a well-known common complication of diabetes in dogs; a study involving 200 dogs reported that 25% of the general diabetic population developed cataracts by 60 days and 50 percent by 170 days post-diagnosis of diabetes mellitus. Furthermore, between 75% and 80% of diabetic dogs developed diabetic cataracts within 370 and 470 days of diagnosis, respectively. Stage 2: Cataract formation: What exactly happens with cataract formation in diabetic dogs: The lens is a metabolically active structure and requires energy. This energy is provided by glucose and utilises an anaerobic pathway catalysed by the enzyme hexokinase to provide this energy. In the case of diabetic dogs, there is excessive glucose in the blood [this also means excessive glucose in the aqueous humour] which leads to overloading of the hexokinase pathway. Excessive lactic acid is the end product of this pathway, and in fact, lowers pH and activates lens proteinase which is already a problem. When the hexokinase pathway is no longer utilised, the glucose is then shunted via the sorbitol pathway [see diagram below]. The aldose reductase enzyme is activated and increased, and the end product sorbitol is produced faster than it can be converted to fructose. Sorbitol has a strong hyperosmotic effect and water is drawn into the lens, swelling the lens fibres, resulting in rupture and vacuole formation within the lens [osmotic stress]. Furthermore, there is an excessive influx of Na+ and Ca2+, activation of proteolytic enzymes and modification of the healthy crystalline lens proteins. These changes in the lens fibre structure cause the opacity which we refer to as a cataract. Regulars I Ophthalmology Column Diabetes, Cataracts and Lens-Induced Uveitis [LIU] – the Terrible Trio Dr Antony Goodhead, Specialist Veterinary Ophthalmologist, Johannesburg and Cape Animal Eye Hospitals, www.animaleyehospital.co.za Science Direct: Chapter 4 - Animal Models in Cataract Research Animal Models for the Study of Human Disease (Second Edition)
RkJQdWJsaXNoZXIy OTc5MDU=