Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and nonperfusion. Diabetic retinal vascular leakage, capillary nonperfusion, and endothelial cell damage are temporary and spatially associated with retinal leukocyte stasis in early experimental diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1) and CD18. Mice deficient in the genes encoding for the leukocyte adhesion molecules CD18 and ICAM-1 were studied in two models of diabetic retinopathy with respect to the long-term development of retinal vascular lesions. CD18-/- and ICAM-1-/- mice demonstrate significantly fewer adherent leukocytes in the retinal vasculature at 11 and 15 months after induction of diabetes with STZ. This condition is associated with fewer damaged endothelial cells and lesser vascular leakage. Galactosemia of up to 24 months causes pericyte and endothelial cell loss and formation of acellular capillaries. These changes are significantly reduced in CD18- and ICAM-1-deficient mice. Basement membrane thickening of the retinal vessels is increased in long-term galactosemic animals independent of the genetic strain. Here we show that chronic, low-grade subclinical inflammation is responsible for many of the signature vascular lesions of diabetic retinopathy. These data highlight the central and causal role of adherent leukocytes in the pathogenesis of diabetic retinopathy. They also underscore the potential utility of anti-inflammatory treatment in diabetic retinopathy.

The very young seedlings of trifoliate orange, and its hybrids with trifoliate leaves as a marker, are usually used as a rootstock for in vitro and in vivo micrografting of citrus to eliminate viruses in spring in temperate regions. In tropical and subtropical regions or in summer, however, the production and use of trifoliate orange seedlings is difficult. Therefore, it is necessary to establish suitable micrografting using efficient Citrus seedlings adapted to these regions and summer. In decapitated seedlings for micrografting, adventitious shoots on the cut end of the epicotyls and shoots from cotyledon axillary buds are often formed. Hence, the potential for adventitious shoot formation and cotyledon axillary shoot formation was firstly studied with decapitated seedlings from 11 Citrus accessions and one Poncirus accession as a control. Mature seeds of the 12 accessions were germinated in vivo and seedlings of various ages (2-, 4-, and 8-week-old, 4-month-old and 8-month-old after germination) were decapitated at three (lower, middle, and upper) positions on the epicotyls. Adventitious shoot formation decreased with increases in the age of seedlings decapitated at eight weeks or 4 months after germination. The percentage of decapitated seedlings forming adventitious shoots was different in different accessions ranging from 0% to 100%, and increased with increases in decapitation height in the epicotyls. It was estimated from these results that 2-week-old seedlings of Natsudaidai, Shiikuwasha, 'Hiradobuntan', 'Variegated Daidai', and trifoliate orange 'Flying Dragon' had higher potential to support the initial growth of adventitious shoots, and cotyledon axillary shoots than the others, and that decapitation at the upper one-third and middle of epicotyls resulted in higher adventitious shoot formation than the lower one-third. In in vivo micrografting of satsuma mandarin on the seedlings of these accessions, Natsudaidai, 'Hirado-buntan', and 'Variegated Daidai' seedlings resulted in high micrografting success rates, whereas 'Kabusu', 'Flying Dragon' and Shiikuwasha seedlings resulted in very low success rates. The success rate decreased with increases in seedling age. It has become clear from these results that there is no relationship between the potential for shoot formation and micrografting success and that the 2-week-old seedlings of Natsudaidai, 'Hirado-buntan' and 'Variegated Daidai' are efficient rootstocks for micrografting.