CB1, a cannabinoid receptor enriched in neuronal tissue, was found in high concentration in retinas of rhesus monkey, mouse, rat, chick, goldfish, and tiger salamander by using a subtype-specific polyclonal antibody. Immunolabeling was detected in the two synaptic layers of the retina, the inner and outer plexiform layers, of all six species examined. In the outer plexiform layer, CB1 was located in and/or on cone pedicles and rod spherules. Labeling was detected in some amacrine cells of all species and in the ganglion cells and ganglion cell axons of all species except fish. In addition, sparse labeling was found in the inner and/or outer segments of the photoreceptors of monkey, mouse, rat, and chick. Using GC/MS to detect possible endogenous cannabinoids, we found 3 nmol of 2-arachidonylglycerol per g of tissue, but no anandamide was detectable. Cannabinoid receptor agonists induced a dramatic reduction in the amplitude of voltage-gated L-type calcium channel currents in identified retinal bipolar cells. The presence and distribution of the CB1 receptor, the large amounts of 2-arachidonylglycerol found, and the effects of cannabinoids on calcium channel activity in bipolar cells suggest a substantive role for an endogenous cannabinoid signaling system in retinal physiology, and perhaps vision in general.

As an example of the burgeoning importance of stem cell therapy, this past month the California Institute for Regenerative Medicine (CIRM) has approved $70 million to create a new network of stem cell clinical trial centers. Much work in the last decade has been devoted to developing the use of autologous and allogeneic adult stem cell transplants to treat a number of conditions, including heart attack, dementia, wounds, and immune system-related diseases. The standard model teaches us that adult stem cells exists throughout most of the body and provide a means to regenerate and repair most tissues through replication and differentiation. Although we have often witnessed the medical cart placed in front of the scientific horse in the development of stem cell therapies outside of academic circles, great strides have been made, such as the use of purified stem cells1 instead of whole bone marrow transplants in cancer patients, where physicians avoid re-injecting the patients with their own cancer cells.2 We...

To date, two cannabinoid receptors, CB1 and CB2, have been cloned. The CB1 receptor has been found in a variety of tissues, particularly in the brain. CB2 receptor mRNA is mainly expressed in the immune system, though one group has found it in mouse cerebellum. Previous immunostaining studies in our lab demonstrated the presence of CB1 receptors in the retina though little evidence exists for the presence of CB2. The putative endogenous ligand for CB2 has been found in retina, however, suggesting that further study of CB2 in retina is warranted. Because glutamate is toxic to retinal ganglion cells in glaucoma and activation of CB2 receptors may be able to protect neurons from glutamate-induced death, we examined the expression of CB2 mRNA in adult rat retina in order to better understand possible neuroprotective mechanisms relevant to glaucoma. Using in situ hybridization, we demonstrated that CB2 cannabinoid receptor messenger RNA was clearly expressed in the adult rat retina, including the somas of retinal ganglion cells. Antisense cRNA probe detected strong signals in the retinal ganglion cell layer, the inner nuclear layer, and the inner segments of photoreceptor cells. Using reverse transcription polymerase chain reaction (RT-PCR) in both rat and mouse tissue, we obtained an RT-PCR product with the same sequence as that reported for CB2 in the GenBank database, thus confirming the presence of CB2 mRNA in retina. The presence of CB2 in retina provides new evidence for the presence of CB2 in the central nervous system (CNS) and an excellent model for its study.

Here we offer a review of the evidence for a hypothesis that a combination of ingestible probiotics, prebiotics, postbiotics, and amino acids will help ameliorate dysbiosis and degeneration of the gut, and therefore promote restoration of nervous system function in a number of neurological indications.