Biodegradable collagen matrix implant vs mitomycin-C as an adjuvant in trabeculectomy: a 24-month, randomized clinical trial

AIM: To verify the safety and efficacy of Ologen (OLO) implant as adjuvant compared with low-dosage mitomycin-C (MMC) in trabeculectomy. METHODS: This was a prospective randomized clinical trial with a 24-month follow-up. Forty glaucoma patients (40 eyes) were assigned to trabeculectomy with MMC or OLO. Primary outcome includes target IOP at ≤21, ≤17, and ≤15 mm Hg; complete (target IOP without medications), and qualified success (target IOP regardless of medications). Secondary outcomes include bleb evaluation, according to Moorfields Bleb Grading System (MBGS); spectral domain optical coherence tomography (SD-OCT) examination; number of glaucoma medications; and frequency of postoperative adjunctive procedures and complications. RESULTS: The mean preoperative IOP was 26.5 (±5.2) in MMC and 27.3 (±6.0) in OLO eyes, without statistical significance. One-day postoperatively, the IOP dropped to 5.2 (±3.5) and 9.2 (±5.5) mm Hg, respectively (P=0.009). The IOP reduction was significant at end point in all groups (P=0.01), with a mean IOP of 16.0 (±2.9) and 16.5 (±2.1) mm Hg in MMC and OLO, respectively. The rates and Kaplan-Meier curves did not differ for both complete and qualified success at any target IOP. The bleb height in OLO group was higher than MMC one (P<0.05). SD-OCT analysis of successful/unsuccessful bleb in patients with or without complete success at IOP ≤17  mm Hg indicated a sensitivity of 83% and 73% and a specificity of 75% and 67%, respectively, for MMC and OLO groups. No adverse reaction to OLO was noted. CONCLUSIONS: Our results suggest that OLO implant could be a new, safe, and effective alternative to MMC, with similar long-term success rate

Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance

Background: The transcription factor Pax6 is expressed by many cell types in the developing eye. Eyes do not form in homozygous loss-of-function mouse mutants (Pax6(Sey/Sey)) and are abnormally small in Pax6(Sey/+) mutants. Eyes are also abnormally small in PAX77 mice expressing multiple copies of human PAX6 in addition to endogenous Pax6; protein sequences are identical in the two species. The developmental events that lead to microphthalmia in PAX77 mice are not well-characterised, so it is not clear whether over- and under-expression of Pax6/PAX6 cause microphthalmia through similar mechanisms. Here, we examined the consequences of over-expression for the eye and its axonal connections. Results: Eyes form in PAX77(+/+) embryos but subsequently degenerate. At E12.5, we found no abnormalities in ocular morphology, retinal cell cycle parameters and the incidence of retinal cell death. From E14.5 on, we observed malformations of the optic disc. From E16.5 into postnatal life there is progressively more severe retinal dysplasia and microphthalmia. Analyses of patterns of gene expression indicated that PAX77(+/+) retinae produce a normal range of cell types, including retinal ganglion cells (RGCs). At E14.5 and E16.5, quantitative RT-PCR with probes for a range of molecules associated with retinal development showed only one significant change: a slight reduction in levels of mRNA encoding the secreted morphogen Shh at E16.5. At E16.5, tract-tracing with carbocyanine dyes in PAX77(+/+) embryos revealed errors in intraretinal navigation by RGC axons, a decrease in the number of RGC axons reaching the thalamus and an increase in the proportion of ipsilateral projections among those RGC axons that do reach the thalamus. A survey of embryos with different Pax6/PAX6 gene dosage (Pax6(Sey/+), Pax6(+/+), PAX77(+) and PAX77(+/+)) showed that (1) the total number of RGC axons projected by the retina and (2) the proportions that are sorted into the ipsilateral and contralateral optic tracts at the optic chiasm vary differently with gene dosage. Increasing dosage increases the proportion projecting ipsilaterally regardless of the size of the total projection. Conclusion: Pax6 overexpression does not obviously impair the initial formation of the eye and its major cell-types but prevents normal development of the retina from about E14.5, leading eventually to severe retinal degeneration in postnatal life. This sequence is different to that underlying microphthalmia in Pax6(+/-) heterozygotes, which is due primarily to defects in the initial stages of lens formation. Before the onset of severe retinal dysplasia, Pax6 overexpression causes defects of retinal axons, preventing their normal growth and navigation through the optic chiasm

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells