Oxidative Stress and the Eye: The Retina

Oxidative Stress and the Eye:
The Retina

*The authors of this article are both founding members of Animal HealthQuest LLC, which is a research and development company dedicated to creating research-driven vision health supplements for companion animals. The authors are also consultants for Animal Necessity LLC, which is a research and development company providing supplements for companion, zoo, and aquatic animals.

Terri McCalla  DVM MS DACVO
Carmen Colitz DVM PhD DACVO               

Too much of a good thing can become a bad thing; cells of the body with the highest need for oxygen also demand exquisitely balanced oxidative stress, or they can self-destruct. The two tissues of the body with the highest demand for oxygen (and thus require a rich blood supply) are the brain (in particular, the occipital cortex which is necessary for vision) and the retina. The eye and brain have evolved to use high levels of oxygen without being destroyed by oxygen, which requires exquisitely orchestrated and balanced oxidative stress.                                                                                          

In order to understand what happens when the retina gets sick, we need to look at what the retina is. The retina is a thin and floppy bit of tissue that looks similar to the membrane on a hard-boiled egg, except that it has blood vessels in it.   But the retina is so much more!  The retina and brain are both derived from the same embryologic cell type. In the fetus, cells that form the spinal cord and brain also form two round hollow balls that protrude from each side of the fetal brain, like balls on the tips of antennae. As the fetus grows, these balls collapse in on themselves to become a double-layered cup, similar to a completely deflated basketball, or a whole pita bread shaped like a saucer. This is called the fetal optic cup, and the two layers of the optic cup lay next to each other to form the two layers of the retina-- neural and retinal pigment epithelium (RPE).  The 'antennae' attaching the optic cup to the brain forms the optic nerve.  Think of the retina and optic nerve as brain tissue.  In fact, just like the brain and spinal cord are bathed in cerebrospinal fluid (CSF), the optic nerve is also bathed in CSF.                                      

The inner layer of the optic cup ends up forming the neural layer of the retina; this is about 10 cells thick and contains rod and cone photoreceptor cells.  Rods and cones are the magical cells that transform light into electrical energy that the optic nerve then sends to the brain to create vision.  Rods help with night vision, and cones help with day vision and color vision.  Over 90% of photoreceptors are rods and the rest are cones.                                    

Rods and cones are long skinny cells in which the "tail" of the cell is packed with membranes that look like stacks of Frisbees, called disc outer segments. These discs are the 'nuclear reactors' that transform light into energy;  this process requires a constant junking (digestion) of old worn-out discs and renewal of fresh new discs.  This digestion is accomplished by the RPE outer layer of the optic cup.  The RPE also protects rods and cones from damage by excessive light, and provides a barrier to protect rods and cones from toxins in the peripheral bloodstream ('blood-retinal-barrier', or BRB). There is a similar barrier of specialized cells that protect the inside of the front half of the eye from toxins in the bloodstream ('blood-aqueous-barrier', or BAB).  These barriers are very similar to the barrier that protects the brain from toxins in the bloodstream ('blood-brain-barrier', or BBB).          

Why is this all so important?  Because many different factors can cause a breakdown in the control of oxidative stress and thus a breakdown in the BRB and/or BAB and retinal health, including aging changes in the RPE and inflammation inside the eye (uveitis).  Inflammation of the retina can cause the RPE to separate from the neural retina, which is the definition of a retinal detachment.  Retinal detachments occur relatively easily because there is a potential space between neural retina and RPE (i.e. the two layers of the fetal optic cup), and a natural tendency for a weakened neural retina to separate and "unzip" from the RPE within this potential space (like peeling apart pita bread). And in humans, aging RPE cells can accumulate byproducts of outer disc digestion that can cause Age-Related Macular Degeneration (ARMD).  Fun fact:  The retinas of domestic animals do not have maculae.  Thus, dogs and cats cannot get macular degeneration.                                                                                          

Retinal detachment is relatively common in dogs and cats; in dogs, it is often genetic but can also be associated with uveitis, trauma, infectious disease, cancer, metabolic disease such as high blood pressure, or following cataract surgery.  In geriatric cats, the most common cause of vision loss is retinal hemorrhage and/or detachment due to high blood pressure (hypertensive retinopathy).                                          

Obviously, loss of retinal function from any cause can result in vision impairment. Just like brain cells, rods and cones and also RPE cells do not regenerate. As animals and humans age, there is a natural loss of photoreceptor function, especially rods.  Thus, night vision suffers in the geriatric animal (Senile Retinal Degeneration).                     

The most common retinal disease in dogs is Progressive Retinal Atrophy (PRA).  This retinal degeneration is genetic, and is present in most breeds of dogs.  The typical patient is 6-8 years of age and is initially presented to the veterinary ophthalmologist with a history of poor night vision that has gotten worse recently.  In most breeds, the disease initially kills rods, resulting in night blindness. However, the cones then slowly die, resulting in a slow loss of day vision.   It has been theorized that the death of rods results in delivery of excessive retinal oxygen-- i.e. that oxygen abounds because there are not enough living rod cells to use it.  This results in oxygen toxicity to cones and a destructive imbalance in oxidative stress with resultant slow death of cones.  Most affected dogs will also develop cataracts (which can be more blinding than the PRA) secondary to toxins from cell death diffusing through the vitreous to sicken the lens.  There is no cure for PRA.                                                                                                                

While the primary focus for PRA is to limit the gene pool by identifying affected dogs and dogs that are carriers for the gene before they are bred, affected animals can be supported with specific antioxidant supplementation to help prolong cone and lens cell survival, utilizing antioxidants known to support retinal and lens cells both in health and in disease.  These antioxidants include grapeseed extract (GSE), lutein, and omega 3 fatty acids. Note:  It should be remembered that GSE is not the same as grapeskin;  grapeskin is toxic to dogs and cats, which is why raisins and grapes should be not given to dogs and cats. 

Thus, animals with retinal degeneration of any cause, including dogs with PRA and cats with hypertensive retiinopathy, may benefit from specific antioxidant support.  One key for brain health is proper antioxidant support, and this is also true for retinal health.