Scientists regenerate neurons in mice with spinal cord injury and optic nerve damage

New research by scientists at the Lewis Katz School of Medicine Temple University (LKSOM) shows, however, that gains in functional recovery from these injuries may be possible, thanks to a molecule known as Lin28, which regulates cell growth. In a study published online in the journal Molecular Therapy, the Temple researchers describe the ability of Lin28 -- when expressed above its usual levels -- to fuel axon regrowth in mice with spinal cord injury or optic nerve injury, enabling repair of the body's communication grid.

"Our findings show that Lin28 is a major regulator of axon regeneration and a promising therapeutic target for central nervous system injuries," explained Shuxin Li, MD, PhD, Professor of Anatomy and Cell Biology and in the Shriners Hospitals Pediatric Research Center at the Lewis Katz School of Medicine at Temple University and senior investigator on the new study. The research is the first to demonstrate the regenerative ability of Lin28 upregulation in the injured spinal cord of animals.

"We became interested in Lin28 as a target for neuron regeneration because it acts as a gatekeeper of stem cell activity," said Dr. Li. "It controls the switch that maintains stem cells or allows them to differentiate and potentially contribute to activities such as axon regeneration."

To explore the effects of Lin28 on axon regrowth, Dr. Li and colleagues developed a mouse model in which animals expressed extra Lin28 in some of their tissues. When full-grown, the animals were divided into groups that sustained spinal cord injury or injury to the optic nerve tracts that connect to the retina in the eye.

Another set of adult mice, with normal Lin28 expression and similar injuries, were given injections of a viral vector (a type of carrier) for Lin28 to examine the molecule's direct effects on tissue repair.

Extra Lin28 stimulated long-distance axon regeneration in all instances, though the most dramatic effects were observed following post-injury injection of Lin28. In mice with spinal cord injury, Lin28 injection resulted in the growth of axons to more than three millimeters beyond the area of axon damage, while in animals with optic nerve injury, axons regrew the entire length of the optic nerve tract. Evaluation of walking and sensory abilities after Lin28 treatment revealed significant improvements in coordination and sensation.

"We observed a lot of axon regrowth, which could be very significant clinically, since there currently are no regenerative treatments for spinal cord injury or optic nerve injury," Dr. Li explained.

One of his goals in the near-term is to identify a safe and effective means of getting Lin28 to injured tissues in human patients. To do so, his team of researchers will need to develop a vector, or carrier system for Lin28, that can be injected systemically and then hone in on injured axons to deliver the therapy directly to multiple populations of damaged neurons.

Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Corona viruses and Ocular Implications in Humans and Animals

A Review ofCoronaviruses and Ocular Implications in Humans and Animals

In December 2019, a unique coronavirus epidemic, caused by the severe acute respiratory syndrome coronavirus – 2 (SARS-CoV-2) emerged from China. This virus causes the coronavirus disease 2019 (COVID-19). Since then, there are anecdotal reports of ocular infection. The ocular implications of human (CoV) infections haven't been widely studied. However, CoVs are known to cause various ocular infections in animals. Clinical entities like conjunctivitis, anterior uveitis, retinitis, and optic neuritis are documented in feline and murine models. This evidence suggesting possible human CoV infection of ocular tissue is surveyed. We hope that this may function a start for further research into the ocular implications of human CoV infections.

CoVs rose to public prominence after the outbreak of the Severe Acute Respiratory Syndrome.The SARS-CoV outbreak was reported to possess infected over 8000 people and resulted in 774 deaths globally. Since then, the Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) has also been within the public spotlight.

A set of recommendations for private protective equipment (PPE) supported the experience of MERS-CoV and SARS-CoV are released.7 This set of advice includes wearing goggles or faceshield for defense against ocular transmission of the CoV.

The Coronavirus Structure and Host:

The CoV name may be a derivative from the Latin word corona which suggests crown. this can be because of the characteristic structure of the virus whereby surface projections on the viral envelope provides it an appearance almost like a crown. The virus may be a single-stranded positive-sense RNA virus with a genome of around 30 kb long. This makes them the most important known RNA viruses. The S-protein is answerable for attachment to host receptors, M protein helps shape the virion particles and binding to nucleocapsid, E-protein plays a job within the assembly and release of particles while N-protein aids with the binding of the genome to a replication-transcription complex which is required for the replication of genomic material.

Human Coronaviruses and also the Evidence for OcularManifestations

There are seven types CoVs known to infect humans

·         Alpha coronavirus 229E

·         Alpha coronavirus NL63

·         Beta coronavirus OC43

·         Beta coronavirus HKU1

·         Beta coronavirus MERS-CoV

·         Beta coronavirus SARS-CoV

·         And Recent SARS-CoV-2(COVID-19)

Feline Coronaviruses and Ocular Manifestations:

The feline CoV (FCoV) is an Alphacoronavirus that affects both domestic and wild cats. Approximately 20–60% of domestic cats are seropositive, while in animal shelters, the seropositive rates can approach almost 90%. FCoVs is further classified into two biotypes which reflect very varied clinical presentations.

·         Feline enteric CoV (FECV)

·         Feline infectious peritonitis virus (FIPV)

In majority of those seropositive cases, the FCoVs exist as FECV. For many of the FECV cases, the infection is typically benign or related to a self-limiting diarrhea. This can be because FECV has been shown to demonstrate tropism to the apical epithelium of the intestinal villi from the tiny intestine to the cecum. As such, FECV shedding in feline feces is answerable for the fecal–oral spread and maintenance of FECV infection in feline populations, explaining the high seropositive rates of the infection.

The ocular manifestation of FIP is probably going because of underlying vasculitis, leading to inflammation of varying ocular segments. During a study that observed FIPV-infected felines and their offspring, 90% of the infected cats had FCoV antigen detected within the conjunctiva. Viral isolates from conjunctival swabs also contained live FCoV which suggest that ocular tissues and secretions were potentially infectious additionally. Furthermore, the initially healthy offspring, after being kept with the infected parents for 100 days, developed recurrent bouts of conjunctivitis. Except for conjunctivitis, ocular manifestations include pyogranulomatous anterioruveitis, choroiditis with detachment of the retina and retinal vasculitis. In general, ocular manifestations of FIPV infection have poor prognosis both visually and systemically.

 Conclusion:

As CoVs can cause ocular infection across different animals, the likelihood of SARS-CoV-2 having ocular implications can't be ignored. However, the examples in animals also highlight that CoVs are a heterogeneous group of viruses that may cause ocular implications through a good sort of mechanisms. A number of these mechanisms are extremely different from those adopted by human CoVs. Nevertheless, there are lessons to be learned by understanding these infections. Firstly, CoVs are capable of manufacturing a good spectrum of ocular manifestations from anterior segment pathologies like conjunctivitis and anterior uveitis to sight-threatening conditions like retinitis and optic neuritis. Secondly, it's going to even be prudent to acknowledge that CoVs also can develop in-vivo mutations which drastically alter the manifestations of the disease.

Given the anecdotal nature of evidence regarding SARS-CoV-2 transmission through ocular tissue, more research must be done to verify its ability to infect ocular tissue and its pathogenic mechanisms. Because the current epidemic continues, an improved understanding of the virus will emerge, hopefully with more emphasis on research into the connection between human CoVs and also the eye. This understanding won't only help to guide infection control measures but also can provide insights on the feasibility of using ocular tissue or perhaps tears as a medium of diagnosis. Meanwhile, ophthalmologists and other health-care workers should still err on the side of caution and still prevent the possible transmission of CoVs through ocular tissue.