Many of us have patients with retinitis pigmentosa; sometimes they come in with the diagnosis, and sometimes we are the ones who discover the hallmarks of the disease. It is a quintessential “a-ha!” moment – when we see the classic bone spiculing in the peripheral retina and remember how the patient made certain comments about trouble seeing at night. But it’s a sad moment because we know how devastating the disease can be and how little we as providers can do to allay the progression.
But what of that hallmark finding, the bone spicule? We think of it classically (besides some obscure subtypes) as sine qua non for a retinitis pigmentosa (RP) diagnosis, but do we stop to think about why the spicule shape happens in the first place?
The word “spicule” refers to a needle-like shape, derived from the Latin word for the tip of a wheat plant. The term bone spicules is used to refer to the type of small cells that are laid down in the formation of new bone matrix. These spicules in bone have a similar shape to the classic pigment finding in RP, thus the name.
Examples of bone spicules.
But why does the retinal pigment epithelium (RPE) change into spicule shape, and why essentially only in this disease? The answer has to do with how RP develops, specifically the order in which the retina begins to fail.
Animal and human models have shown that bone spicules form only in areas of the retina where photoreceptors are missing. The first structure to fail in RP is the rod outer segment, followed by the rod inner segment and then the outer nuclear layer. This happens to region after region in the retina, until much of the rod ring is lost. Then the disease can often progress to cones.
But in most cases, the inner retina is left intact in the early and mid-stages of the disease. And by the mid stage of the disease, in affected areas of the retina, the inner retina has now come in contact with the RPE because the outer retina has been lost. A kind of downwards or posterior migration of the inner retina occurs, and retinal vessels from the inner retina can make direct contact with the RPE.
This is the trigger that has been identified for bone spicule formation – the retina vessel/RPE touch. Migration of the RPE cells occurs without fail along these vascular networks of the inner retina, starting in the interstitial space and then cuffing the vessels.
So the fact that spicules have their shape from retinal blood vessels is interesting, but what’s more interesting is why they migrate at all. Why are RPE cells attracted to these retinal vessels in areas of the retina that have lost their photoreceptors?
The answer is an interesting discovery in how the body can sense its own defects and attempt to repair itself. When photoreceptors die, retinal integrity is altered. The outer retina loses its function and, therefore, creates a reduced vascular demand on the choriocapillaris and, to a lesser extent, the retinal arteries.
Examples of bone spicules.
Source: Rett D
But as the condition worsens, the vascular demand lessens and starts another classic RP finding: attenuation of the retinal arteries. And if the retinal arteries attenuate past a certain point, their tight junctions break down, and the inner retina becomes hypoxic as well, creating attenuation of all layers of the retina and a general meltdown of a previously well-ordered equilibrium.
What the RPE cells are doing when they migrate along the interstitial spaces surrounding the retinal vessels are creating new tight junctions in order to recreate the blood-retinal barrier and keep the inner retinal thickness intact, despite the loss that the outer retina has already suffered. Mouse models have found that, indeed, when RPE cells detach themselves from Bruch’s membrane and travel to a spot along a retinal vessel, they always align their basal side toward the vessel. This suggests the RPE is forming tight junctions around the retinal vessels like it was at the choriocapillaris junction. In fact, ultrastructural imaging has shown the RPE cells seal the vessels with tight junction linkage, deposit perivascular extracellular matrix and induce fenestrations in the vascular endothelium of the cuffed vessels. The RPE cells are essentially turning damaged retinal vessels into something very similar to vessels of the choriocapillaris, to save the inner retina.
It’s amazing how much research has been done on RP and how much we know about the disease, yet still a significant treatment eludes us. Much of the work recently has been on gene therapy and stem cell transplantation, which seem to show some optimism with RP. I hope we can make progress soon and help out these little RPE cells, doing yeoman’s work trying to save the inner retina one small area at a time.
Hartong DT, et al. Lancet. 2006;368:1795-1809.
Ida H, et al. Invest Ophthalmol Vis Sci. 2003;44:5430-5437.
Jaissle GB, et al. Graefes Arch Clin Exp Ophthalmol. 2010;248(8):1063-1070. doi: 10.1007/s00417-009-1253-9.
Ryan SJ. Retina. 4th ed. Elsevier-Mosby; 2006.